Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

[Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury].

Objective: To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury. Methods: Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ(2) test or t-test was used for statistical analysis. Results: Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference (χ(2) = 9.975 0, P = 0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference (χ(2) = 0.593 5, P = 0.441 1). Conclusion: Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

Using transvaginal ultrasonography and MRI to evaluate ovarian volume and follicle count of infertile women: a comparative study.

AIM: To compare two-dimensional (2D) transvaginal ultrasonography (TVUS) and 2D/three-dimensional (3D) magnetic resonance imaging (MRI) in estimating ovarian volume and follicle count. MATERIALS AND METHODS: The ovarian volume (OV) and follicle count (FC) of 84 women with infertility were evaluated by 2D TVUS and 2D/3D MRI. Bland-Altman analysis was used for comparison. RESULTS: The OV from 3D MRI was 0.50 ml (95% confidence interval [CI], 0.25-0.74, p<0.001) smaller than that by 2D TVUS. OV from 2D MRI was 2.65 ml (95% CI, 2.36-2.95, p<0.001) and 3.15 ml (95% CI, 2.77-3.53, p<0.001) smaller than that from 3D MRI and 2D TVUS, respectively. The FC1-9 mm and total follicle count (tFC) estimated by 2D TVUS were 7.81 (95% CI, 6.96-8.66, p<0.001) and 7.82 (95% CI, 6.97-8.67) smaller than those from 2D MRI, respectively. Further analysis showed that 2D TVUS detected lower FC1-3 mm but higher FC4-6 mm than 2D MRI. No significant difference was shown in the results of FC7-9 mm and FC ≥ 10 mm. CONCLUSION: In women with infertility, 2D MRI underestimated OV as compared with 2D TVUS. OV from 3D MRI was lower but very close to that from 2D TVUS. For patients unsuitable for TVUS, 3D MRI is recommended for OV evaluation. 2D TVUS underestimated FC1-9 mm and tFC compared with 2D MRI. In fertility counselling and research, 2D MRI is a useful alternative to TVUS when an accurate FC is needed.

New α-Emitting Isotope

A new α-emitting isotope ^{214}U, produced by the fusion-evaporation reaction ^{182}W(^{36}Ar,4n)^{214}U, was identified by employing the gas-filled recoil separator SHANS and the recoil-α correlation technique. More precise α-decay properties of even-even nuclei ^{216,218}U were also measured in the reactions of ^{40}Ar, ^{40}Ca beams with ^{180,182,184}W targets. By combining the experimental data, improved α-decay reduced widths δ^{2} for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N=126 are deduced. Their systematic trends are discussed in terms of the N_{p}N_{n} scheme in order to study the influence of proton-neutron interaction on α decay in this region of nuclei. It is strikingly found that the reduced widths of ^{214,216}U are significantly enhanced by a factor of two as compared with the N_{p}N_{n} systematics for the 84≤Z≤90 and N<126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the π1f_{7/2} and ν1f_{5/2} spin-orbit partner orbits, which is supported by the large-scale shell model calculation.

[Reoperation rate and related factors in patients with Crohn's disease].

Objective: To analyze the cumulative reoperation rate of postoperative Crohn's disease (CD) patients and investigate the operation reasons and the effects of drugs on surgical recurrence. Method: Patients with Crohn's disease who had undergone intestinal resection from January 2000 to March 2020 in Peking Union Medical College Hospital were enrolled. Patients were divided into reoperation and non-reoperation group according to whether they had a second operation. And the basic characteristics and the reasons for the primary and second operation were retrospectively analyzed. Meanwhile, patients were divided into low-risk reoperation group and high-risk group based on risk stratification. Kaplan-Meier methods were performed to analyze the cumulative surgical recurrence rate and to compare the recurrence rate in different risk stratification and chi-square tests was used to analyze the effects of different maintenance drugs on reoperation. Result: A total of 160 patients were enrolled in the study. There were 110 males and 50 females, and the age at first operation was (35.6±14.1) years old. There were 40 patients in the reoperation group and 120 patients in the non-reoperation group. According to univariate analysis, the proportion of male gender(P=0.030), penetrating phenotype(P<0.001), history of appendectomy before the primary surgery(P=0.035) and no postoperative maintenance therapy (P<0.001) were higher in surgical recurrence group. In terms of the operation reasons, intestinal obstruction accounted for the highest proportion in the primary operation (26.9%, 43/160), while the intestinal fistula was the most common reason for reoperation (42.5%, 17/40). After the primary surgery, the cumulative reoperation rates at 1, 3, 5 and 10 years were 5.9% (9 cases), 12.3% (17 cases), 21.8% (25 cases) and 37.6% (34 cases), respectively. The ten years cumulative reoperation rate of the high-risk group was 42.8% (31 cases), which was much higher than that of low-risk group (19.8%, 3 cases), and the difference was statistically significant (P=0.006). There was no statistically significant difference in the surgical recurrence rate of low-risk group patients(P=0.076)whether maintenance therapies were added or not, while the recurrence rate of high-risk group patients who did not receive maintenance therapy was higher than those who received immunosuppressant with or without (±) 5-aminosalicylic acid (ASA) (P=0.001) and biological agent±5-ASA (P=0.001), and the difference was statistically significant. Conclusion: Patients with CD are still at risk of reoperation after surgery. Immunosuppressive agents and biologics can prevent patients from reoperation in high-risk groups.

[Establishment and application of HPLC-MS/MS method for detecting m6A level in RNA].

Objective: Explore the establishment of a fast, stable and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for detecting the level of m6A modification in RNA and its application. Methods: The degree of m6A in RNA can be expressed as the ratio of m6A and adenosine (A) in concentration, which can be determined by ESI source positive ion multiple reaction monitoring (MRM) mode. The established method was verified by analyzing three quality control samples (m6A: 4, 40, 400 nmol/L; A: 40, 400, 4 000 nmol/L) with three different concentrations of low, medium, and high. The method was used to detect the degree of m6A in RNA from mouse spleen T cells treated in different ways. The t test was used to compare the differences between the two groups of data. Results: The established method had a good Linearity (R2>0.99) in a range of 1-500 nmol/L for m6A and 10-5 000 nmol/L for A. The limit of detection (LOD) was 1 nmol/L for m6A and 10 nmol/L for A. The recoveries were between 98.9% and 116.5%. The intra-day (n=5) RSDs and the inter-day (n=15, 5 days) RSDs were 2.4%-9.5% and 4.4%-9.6%, respectively. And this method was used to detect the degree of m6A in the RNA from mouse spleen T cells cultured in different conditions. The results showed that the m6A modification level in the RNA of primary CD8+T cell was 0.271 5±0.017 9, and the m6A modification level in the RNA of primary CD8+T cell with IL-27 was 0.251 7±0.015 0, indicating that primary CD8+T cells have a higher level of RNA methylation. Conclusion: This research has established a fast, simplemethylation degree in RNA with HPLC-MS/MS. This method is easy to be popularized and is suitable for the detection of large quantity of samples, and of great significance in analyzing the relationship between methylation and diseases.

[Correlation analysis between ICG-R15 and modified Scheuer score in liver tissues of patients with hepatitis B e antigen-positive/negative chronic hepatitis B].

Objective: To analyze the correlation between indocyanine green retention rate at 15 minutes (ICG-R15) and modified Scheuer score in liver tissues of patients with hepatitis B e antigen-positive/negative chronic hepatitis B (CHB), and further explore the indocyanine green clearance test (ICGCT) applied value in judging the progress of CHB-related liver disease. Methods: 407 HBeAg (+) / HBeAg (-) CHB inpatients with normal or slightly elevated serum alanine aminotransferase (ALT) [< 2 times the upper limit of normal (ULN)] and modified Scheuer score were collected, and divided into mild liver disease group (M group, 131 cases, modified Scheuer score < G2S2) and progressive liver disease group (A group, 276 cases, modified Scheuer score≥G2 and / or S2). Furthermore, the groups were sub-divided into HBeAg (+) - M group, HBeAg (-) - M group, HBeAg (+) - A group and HBeAg (-) - A group. The correlation between ICG-R15 and modified Scheuer score was analyzed retrospectively. The data were analyzed by SPSS 24.0 software. Results: Basic clinical characteristics: Among the 407 CHB cases with normal or mildly elevated serum ALT, 171 were HBeAg(+) CHB and 236 were HBeAg(-) CHB. The baseline mean serum HBV DNA was higher in HBeAg(+) CHB patients [(6.06 ± 1.95) log10IU/ml] than HBeAg(-) CHB patients [(3.60±1.37)log10IU/ml (P = 0.000)]. Included patients ICG-R15 detection characteristics: (1) The baseline mean value of ICG-R15 was not statistically significant between the two groups of HBeAg(+) CHB and HBeAg(-) CHB, and was basically within the normal range (< 10%); (2) Comparison of ICG-R15 baseline mean value among the subgroups showed that the patients in the HBeAg(+)-A group/HBeAg(-)-A group were higher than the HBeAg(+)-M group/HBeAg(-)-M group patients, and the difference was statistically significant (P = 0.013/P = 0.000). Included patients' correlation analysis between ICG-R15 and modified Scheuer score: (1) ICG-R15 and modified Scheuer score had shown weak positive correlation with inflammatory activity grade (g) in HBeAg (+) / HBeAg (-) CHB (r = 0.237, P = 0.002); r = 0.244, P = 0.000); (2) There was a weak positive correlation between ICG-R15 and fibrosis stage (s) in HBeAg (+) / HBeAg (-) CHB (r = 0. 254, P = 0; r = 0.225, P = 0.001). Included patients ICG-R15 predictive value for the severity of liver histological progression: when the cut-off value of ICG-R15 was 5.1%, the area under the receiver operating characteristic curve from M group to A group was 0.601 (P = 0.001) for predicting HBeAg (+) / HBeAg (-) CHB patients. Conclusion: ICG-R15 is positively correlated with the modified Scheuer score of liver tissue in HBeAg (+)/HBeAg (-) CHB patients with normal or slightly elevated ALT. In addition, when the cut-off value of ICG-R15 was 10%, it could not accurately reflect the effective hepatocyte reserve function of HBeAg (+) / HBeAg (-) CHB patients with normal or slightly elevated ALT. Importantly, when the cut-off value of ICG-R15 is 4.0% ~ 5.0%, it may have predictive value for liver disease progression to modified Scheuer score ≥ G2 and / or ≥S2 in HBeAg (+) / HBeAg (-) CHB patients with normal or slightly elevated ALT.

[Veracity of using a visual chart with a testing distance of 2.5 meters for measurement of distance visual acuity in teenagers].

Objective: To compare the results of visual acuity testing for teenagers with visual acuity charts designed at 2.5-meter and 5-meter distances, and to investigate the accuracy of the 2.5-meter visual acuity chart. Methods: It was a self-control study. A total of 227 teenagers (454 eyes) with ametropia who came to the ophthalmic clinic of Peking Union Medical College Hospital from March 2019 to September 2019 were included. There were 123 males and 104 females aged (11.74±3.26) years. The vision examiners were trained in the same testing environment and passed the consistency test. Distance visual acuity of all participants was tested with charts designed at 2.5 meters and 5 meters in a 10-minute interval. According to the age (7-9, 10-12, 13-15 and 16-18 years old) and visual acuity (1.00-0.52, 0.40-0.30 and 0.22-0.10), the results of two kinds of visual acuity charts were compared. The testing order of the two visual charts was randomly determined. The visual acuity results were converted into logMAR values and compared. Paried t-student test was used to compare the difference between two charts, and Pearson correlation test was used to explore the correlation between the results of two charts. Results: The visual acuity of the right eye was 0.37±0.24 (logMAR) at 2.5 meters and 0.50±0.26 (logMAR) at 5 meters. The distance visual acuity measured with the 2.5-meter visual acuity chart was better (t=16.19, P<0.01). The visual acuity of the left eye was 0.36±0.23 (logMAR) at 2.5 meters and 0.45±0.23 (logMAR) at 5 meters (t=11.71, P<0.01). The differences between two charts were larger among teenagers with lower visual acuity (r=0.387,P<0.01). Conclusion: Under the same test conditions, the distance visual acuity measured with a 2.5-meter chart was significantly better than a 5-meter chart. The visual acuity chart designed at 2.5 meters was not an appropriate tool to measure distance vision in adolescents. (Chin J Ophthalmol, 2021, 57: 122-125).

Short-Lived α-Emitting Isotope

A new, very short-lived neutron-deficient isotope ^{222}Np was produced in the complete-fusion reaction ^{187}Re(^{40}Ar,5n)^{222}Np, and observed at the gas-filled recoil separator SHANS. The new isotope ^{222}Np was identified by employing a recoil-α correlation measurement, and six α-decay chains were established for it. The decay properties of ^{222}Np with E_{α}=10016(33) keV and T_{1/2}=380_{-110}^{+260} ns were determined experimentally. The α-decay systematics of Np isotopes is improved by adding the new data for ^{222}Np, which validates the N=126 shell effect in Np isotopes. The evolution of the N=126 shell closure is discussed in the neutron-deficient nuclei up to Np within the framework of α-decay reduced width.

[Association of age-related white matter hyperintensity with brain atrophy and cognitive impairment in patients with Parkinson's disease].

Objective: To investigate the association of age-related white matter hyperintensity (WMH) with brain atrophy and cognitive impairment in patients with Parkinson's disease (PD). Methods: Consecutive samples of a prospective PD cohort with complete 3-dimensional magnetic resonance imaging in the Department of Movement Disorders in Beijing Tiantan Hospital, Capital Medical University, from October 2018 to August 2019 was retrospectively analyzed. Cognition was evaluated by Mini-Mental State Scale (MMSE) and Montreal Cognitive Assessment (MoCA). The severity of WMH was semi-quantitatively measured by Fazekas scale (0-6 points), and the mean cortical thickness and thalamus volume were calculated by FreeSurfer software. The demographic and disease characteristics, the severity of WMH, the mean cortical thickness and thalamus volume were respectively compared between PD patients with and without dementia. Moreover, univariate and multivariate generalized linear models were used to analyze the correlation of the severity of WMH with brain atrophy and MoCA. Results: A total of 225 patients with PD were included in the study, with a median age of 66 years old. Comparisons between groups suggested that patients with dementia were with severer WMH, older, and had lower levels of serum cholesterol and low-density lipoprotein and more reduced mean cortical thickness than those without dementia (all P<0.05), but no significant difference in the thalamus volume was found between the two groups. The generalized linear model showed that the cognitive impairment of PD patients was significantly correlated with WMH (ß=-0.021, 95%CI:-0.040--0.002, P=0.032), but independent of age, cortical thickness, and levels of serum cholesterol and low-density lipoprotein. Conclusion: WMH may worsen PD cognitive impairment independent of brain atrophy. Clinical prevention and treatment of cerebral small vessel disease may have protective effects on cognitive function in patients with PD.

[Predictive value of neutrophil/lymphocyte ratio on myocardial injury in severe COVID-19 patients].

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.

New Isotope

A new short-lived neutron-deficient isotope ^{220}Np was synthesized in the fusion-evaporation reaction ^{185}Re(^{40}Ar,5n)^{220}Np at the gas-filled recoil separator SHANS. Based on the measurement of the correlated α-decay chains, the decay properties of ^{220}Np with E_{α}=10040(18) keV and T_{1/2}=25_{-7}^{+14} µs were determined, which are in good agreement with theoretical predictions. From the new experimental results coupled with the recently reported α-decay data of ^{219,223}Np, the α-decay systematics for Np isotopes around N=126 was established, which allows us for the first time to test the robustness of the N=126 shell closure in Z=93 Np isotopes. The results also indicate that, in the region of nuclei with Z≥83, the proton drip line has been reached for all odd-Z isotopes up to Np.

One cell one niche: hematopoietic microenvironments constructed by bone marrow stromal cells with fibroblastic and histiocytic features.

Hematopoietic microenvironments have been extensively studied, especially focusing on regulation of hematopoietic stem cells (HSCs) in HSC niche following progress of molecular biology in resent years. Based on prior morphological achievements from 1970s, the characteristics of cellular compartments and bone marrow stromal cells (BMSCs) were studied ultrastructurally in human and mice bone marrow in the present study. The samples, human bone marrow granules, were collected from bone marrow aspirations (BMAs) of 20 patients with hematocytopenia and isolated BMSCs were found undesignedly in nucleated cells of BMAs of the patients. Femoral bone marrow samples were collected from 6-week-old three sacrificed mice. Detailed images illustrated maturing hematopoietic cells harbored individually in honeycomb-like microenvironment constituted by BMSCs that shared of fibroblastic and histiocytic characteristics in hematopoietic microenvironments of human and mice bone marrow.

Genetic study of early-onset Graves' disease in the Chinese Han population.

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1-Mb region of the FOXP3 gene, and 20 validated GD-risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region-rs4947296-was more strongly correlated with early-onset GD than non-early-onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤20 years.

[A prognostic model for assessment of outcome of root canal treatment in teeth with pulpitis or apical periodontitis].

OBJECTIVE: To present a prognostic model for evaluating the outcome of root canal treatment in teeth with pulpitis or apical periodontitis 2 years after treatment. METHODS: The implementation of this study was based on a retrospective study on the 2-year outcome of root canal treatment. A cohort of 360 teeth, which received treatment and review, were chosen to build up the total sample size. In the study, 143 teeth with vital pulp and 217 teeth with apical periodontitis were included. About 67% of the samples were selected randomly to derive a training date set for modeling, and the others were used as validating date set for testing. Logistic regression models were used to produce the prognostic models. The dependent variable was defined as absence of periapical lesion or reduction of periapical lesion. The predictability of the models was evaluated by the area under the receiver-operating characteristic (ROC) curve (AUC). RESULTS: Four predictors were included in model one (absence of apical lesion): pre-operative periapical radiolucency, canal curvature, density and apical extent of root fillings. The AUC was 0.802 (95%CI: 0.744-0.859). And the AUC of the testing date was 0.688. Only the density and apical extent of root fillings were included to present model two (reduction of apical lesion). The AUC of training dates and testing dates were 0.734 (95%CI: 0.612-0.856) and 0.681, respectively. As predicted by model one, the probability of absence of periapical lesion 2 years after endodontic treatment was 90% in pulpitis teeth with sever root-canal curvature and adequate root canal fillings, but 51% in teeth with apical periodontitis. When using prognostic model two for prediction, in teeth with apical periodontitis, the probability of detecting lesion reduction with adequate or inadequate root fillings was 95% and 39% 2 years after treatment. CONCLUSION: The pre-operative periapical status, canal curvature and quality of root canal treatment could be used to predict the 2-year outcome of root canal treatment.

[The significances of peripheral neutrophils CD(55) and myeloperoxidase expression in patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody associated vasculitis].

Objective: To investigate the expression of CD(55) and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation. Methods: Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study. The CD(55) on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry. Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA. The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3). The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis. Results: (1)The mean fluorescence intensity(MFI) of CD(55) expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9, P=0.033]. Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L, P<0.001; 35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L, P<0.001], respectively. However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0, P=0.003) . (2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO(r=-0.710, P<0.001) and Ba (r=-0.589, P=0.001). Moreover, serum MPO was positively associated with serum Ba(r=0.691, P<0.001). Membrane intensity of CD(55) on neutrophils was positively correlated with patient age (r=0.514, P=0.001), C reactive protein (r=0.376, P=0.018), peripheral neutrophils count (r=0.485, P=0.001) and BVAS-V3 (r=0.484, P=0.002), whereas negative correlation between membrane CD(55) and disease duration was seen (r=-0.403, P=0.01). (3) The result of multiple linear regression analysis showed there was statistically significant positive correlation between MFI of CD(55) expressed on neutrophils and BVAS-V3 (ß=0.001, P=0.027). Conclusions: In MPO-AAV, CD(55) expression on neutrophils is markedly enhanced, which is one of the independent risk factors related to disease activity. It might protect neutrophils from attacking AAV, CD(55) expression on neutrophils is markedly enhanced, which is one of the independent risk factors related to disease activity. It might protect neutrophils from attacking by complement alternative pathway. Activated neutrophils release more MPO and lysosome to intensify the inflammation reaction and aggravate the disease. Thus CD(55) might become a new potential target for the treatment of this disease in the future.

[Exploratory study of circulating tumor DNA detection in early breast cancer: an analysis of 75 next-generation sequencing results].

Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed. The correlation between mutations and clinic-pathological factors was evaluated by χ(2) test or Fisher's exact test. Results: Seventy-five patients were enrolled in this study. All patients were female and aged from 31 to 88 years with median age of 58 years. All patients' clinic-pathological records were complete. Sixty-four mutations in 18 genes (ALK, BCR, ERBB2, ROS1, PDGFRA, EGFR, FGFR2, CYP1B1, CALR, CASP7, BRAF, FGFR1, FGFR3, MET, NRAS, PTEN, KIT, SOD2) were detected in 47 (62.7%) among all 75 patients.Exons were captured in 10 genes, and mutations in 2 of 3 genes analyzed were clustered. Gene mutations were not correlated with menopausal status, histological type, primary tumor (T), regional lymph nodes (N), TNM stage, histological grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, Ki-67 and molecular subtype (all P>0.05). Conclusion: Circulating tumor DNA sequencing by next-generation sequencing was useful for detecting breast cancer-related mutations.

Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a prospective study.

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association.

[Application of diffusion-weighted intravoxel incoherent motion imaging in diagnosis of renal cell carcinoma subtypes].

OBJECTIVE: To evaluate the value of parameters derived from intravoxel incoherent motion diffusion-weighted magnetic resonance imaging in differentiating histopathological subtypes of renal cell carcinoma (RCC). METHODS: Between May 2014 and December 2015, a total of 69 patients who were surgically and pathologically diagnosed as renal cell carcinoma were recruited for the study. We examined 61 clear cell RCC (ccRCC), and 8 non-clear cell carcinoma (non-ccRCC, including 7 chromophobe RCC and 1 papillary RCC). All the ccRCC were divided into well differentiated group (n=46), moderately differentiated group (n=8), and poorly differentiated group (n=7). In addition to routine renal magnetic resonance imaging examination performed on a 3.0-Tesla MR system, all patients were imaged with axial intravoxel incoherent motion diffusion-weighted imaging. Using biexponential model, we calculated the diffusion coefficient (D), pseudodiffusion coefficient (D(*)), and perfusion fraction (f). RESULTS: The D and f values of the ccRCC were higher (each P<0.05) than that for non-ccRCC [D (1.29±0.30)×10(-3)mm(2)/s, D(*) (42.92±20.21)×10(-3)mm(2)/s, and f (35.71±6.61)% versus D (0.78±0.23)×10(-3)mm(2)/s, D(*) (32.60±11.33)×10(-3)mm(2)/s, and f (21.52±8.44)% ]. In the well differentiated group of ccRCC, we found D of (1.36±0.29)×10(-3)mm(2)/s, D(*) (38.39±18.51)×10(-3)mm(2)/s, and f (36.40±6.96)%. The D, D(*,) f values of moderately differentiated lesions were (1.10±0.24)×10(-3)mm(2)/s, (59.90±20.23)×10(-3) mm(2)/s, and (32.88±4.02)%, respectively, those of the poorly differentiated group were (1.03±0.16)×10(-3)mm(2)/s, (53.28±18.74)×10(-3)mm(2)/s, and (34.42±6.21)%. The well differentiated group of ccRCC showed a higher D value than the moderately differentiated and poorly differentiated groups (each P<0.05). D(*) values were significantly lower for the well differentiated group than for the moderately differentiated group (P<0.05). The sensitivity and specificity of D values were 90.2% and 87.5% when focusing on the differentiation of ccRCC. For the diagnosis of ccRCC, the sensitivity and specificity of f values were 98.4% and 75.0%, respectively. CONCLUSIONS: IVIM-DWI can provide certain reliable value in evaluating pathological subtype and differentiation degree of renal cell carcinomas. D and f values are useful to distinguish ccRCC from non-ccRCC. D value is also promising for estimating the differentiation degree of ccRCC, and to indicate the biological behavior of RCC.