[Pseudocarcinomatous hyperplasia of the fallopian tube: a clinicopathological analysis of sixteen cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pseudocarcinomatous hyperplasia of the fallopian tubes. Methods: Sixteen cases of pseudocarcinomatous hyperplasia of the fallopian tubes diagnosed at Obstetrics and Gynecology Hospital of Fudan University from January 2011 to January 2024 were collected.The pathological sections were reviewed, the clinical and pathological data were consulted, and immunohistochemical examination was conducted along with follow-up. Results: The patients were aged from 19 to 57 years, with an average age of 41 and a median age of 38. Among the 16 cases, 4 were located in the right fallopian tubes, 6 in the left fallopian tubes, while the remaining cases presented bilaterally. The general manifestations were tubal edema, crispness and purulent secretion in the lumen. Morphologically, the fallopian tube mucosa exhibited a significant infiltration of neutrophils, lymphocytes and plasma cells. The epithelial cells of the fallopian tube displayed evident proliferation, stratification and disorganized arrangement leading to formation of small glandular cavity with back-to-back, fissure-like and sieve-like structures. Immunohistochemical analysis revealed positivity for CK7 and WT1, along with wild-type p53 expression, Ki-67 index ranged from 5% to 20%. During the follow-up period ranging from 1 to 156 months, all the patients remained free of disease. Conclusions: Pseudocarcinomatous hyperplasia of the fallopian tube is a rare non-neoplastic lesion, which can lead to epithelial hyperplasia and atypical hyperplasia. The most important significance of recognizing this lesion lies in avoiding misdiagnosis of fallopian tube cancer during intraoperative and postoperative pathological examination. This ensures that clinicians can administer correct clinical interventions.

[Clinicopathological analysis of primary gastric (gastrointestinal)-type mucoglandular lesion of endometrium].

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.

[Construction of a nomogram prediction model for pathological complete response (pCR) of ipsilateral supraclavicular lymph node after neoadjuvant chemotherapy for breast cancer with first diagnosis of ipsilateral supraclavicular lymph node metastasis].

Objective: To develop a predictive model for pathologic complete response (pCR) of ipsilateral supraclavicular lymph nodes (ISLN) after neoadjuvant chemotherapy for breast cancer and guide the local treatment. Methods: Two hundred and eleven consecutive breast cancer patients with first diagnosis of ipsilateral supraclavicular lymph node metastasis who underwent ipsilateral supraclavicular lymph node dissection and treated in the Breast Department of Henan Cancer Hospital from September 2012 to May 2019 were included. One hundred and forty two cases were divided into the training set while other 69 cases into the validation set. The factors affecting ipsilateral supraclavicular lymph node pCR (ispCR)of breast cancer after neoadjuvant chemotherapy were analyzed by univariate and multivariate logistic regression analyses, and a nomogram prediction model of ispCR was established. Internal and external validation evaluation of the nomogram prediction model were conducted by receiver operating characteristic (ROC) curve analysis and plotting calibration curves. Results: Univariate logistic regression analysis showed that Ki-67 index, number of axillary lymph node metastases, breast pCR, axillary pCR, and ISLN size after neoadjuvant chemotherapy were associated with ispCR of breast cancerafter neoadjuvant chemotherapy (P<0.05). Multivariate logistic regression analysis showed that the number of axillary lymph node metastases (OR=5.035, 95%CI: 1.722-14.721, P=0.003), breast pCR (OR=4.662, 95%CI: 1.456-14.922, P=0.010) and ISLN size after neoadjuvant chemotherapy (OR=4.231, 95%CI: 1.194-14.985, P=0.025) were independent predictors of ispCR of breast cancer after neoadjuvant chemotherapy. A nomogram prediction model of ispCR of breast cancer after neoadjuvant chemotherapy was constructed using five factors: number of axillary lymph node metastases, Ki-67 index, breast pCR, axillary pCR and size of ISLN after neoadjuvant chemotherapy. The areas under the ROC curve for the nomogram prediction model in the training and validation sets were 0.855 and 0.838, respectively, and the difference was not statistically significant (P=0.755). The 3-year disease-free survival rates of patients in the ispCR and non-ispCR groups after neoadjuvant chemotherapy were 64.3% and 54.8%, respectively, with statistically significant differences (P=0.024), the 3-year overall survival rates were 83.8% and 70.2%, respectively, without statistically significant difference (P=0.087). Conclusions: Disease free survival is significantly improved in breast cancer patients with ispCR after neoadjuvant chemotherapy. The constructed nomogram prediction model of ispCR of breast cancer patients after neoadjuvant chemotherapy is well fitted. Application of this prediction model can assist the development of local management strategies for the ipsilateral supraclavicular region after neoadjuvant chemotherapy and predict the long-term prognosis of breast cancer patients.

[Mechanism of Mycobacterium tuberculosis on interleukin-6 receptor 3'-untranslated region methylation in CD4+T cells].

Objective: To investigate the role and mechanism of DNA methylation in Mycobacterium tuberculosis (MTB lysate) -induced downregulation of interleukin-6 receptor(IL-6R) expression in CD4+T cells. Methods: A prospective study was conducted. Bisulfite sequencing (BSP) was applied to determine the methylation levels of CpG island in IL-6R promoter region and 3'untranslated region (3'UTR) region in CD4+T cells from peripheral blood mononuclear cells (PBMC) of control group (healthy person, n=10) and TB group (tuberculosis patients, n=10) in Shenzhen Third People's Hospital between 2019 and 2020. Quantitative reverse transcription-PCR (RT-qPCR) and Western blotting were used to detect the expression of IL-6R, DNMT1, DNMT3A and DNMT3B in MTB lysate-stimulated CD4+T cells and Jurkat E6-1 cells. Furthermore, PBMC in control group and Jurkat E6-1 cells activated by anti-CD3/CD28 antibody were stimulated by MTB lysates to detect the methylation levels of CpG island and IL-6R and DNMT expression. Transcriptional activity of differently methylation regions of IL-6R 3'UTR was detected by using luciferase reporter gene system. Results: IL-6R expression in TB group was lower than that in control group, but DNMT1 and DNMT3B expressions were higher than those in control group in CD4+T cells isolated from PBMC. There was no significant difference in the methylation rate of IL-6R promoter CpG island of CD4+T cells between control and TB group. However, the methylation rates of CpG island in 3'UTR region were significantly higher (P<0.001) in TB (69.5%±3.4%), compared with control (54.3%±4.7%). Besides, IL-6R expression was lower than unstimulated, while DNMT1 and DNMT3B expression was higher than unstimulated after MTB lysate-stimulation of activated control PBMC in vitro. The methylation rate of CpG island in IL-6R 3'UTR region of CD4+T cells increased from 58.8%±11.6% to 79.4%±10.9% (P<0.001) after MTB lysate-stimulated PBMC of the control. The same results were observed in the MTB lysate-stimulated CD4+T cells isolated from PBMC in control and Jurkat E6-1 cell line. Furthermore, IL-6R expression after co-treatment of the DNA methyltransferase inhibitor decitabine (5-aza) with MTB lysate was higher than that stimulated by MTB lysate alone. In addition, the methylation levels of CpG islands in the 3' UTR region of IL-6R were lower than those stimulated by MTB lysates alone after co-treatment of the DNA methyltransferase inhibitor decitabine (5-aza) with MTB lysates. The transcriptional activity of the fully unmethylated IL-6R 3'UTR CpG island reporter gene was higher than that of the fully methylated IL-6R 3'UTR CpG island. Conclusions: MTB lysates stimulation inhibited IL-6R expression transcriptionalely as well as on the protein level by inducing hypermethylation of CpG island in IL-6R 3'UTR region of CD4+T cells. The hypermethylation of CpG island in IL-6R 3'UTR region of CD4+T cells induced by MTB may be related to the increased expression of DNMT1 and DNMT3B.

[Screening and preliminary validation of biomarkers in sputum-negative pulmonary tuberculosis based on positron emission tomography/computed tomography and transcriptomics].

Objective: To screen and perform preliminary clinical validation of biomarkers of activity based on positron emission tomography/computed tomography (PET-CT) and transcriptomics in sputum-negative pulmonary tuberculosis lesion tissue. Methods: Nine patients with sputum-negative pulmonary tuberculosis treated surgically at the Shanghai Public Health Clinical Center for Thoracic Surgery from January 1, 2017 to December 31, 2019 were retrospectively collected as the discovery group, including four males and five females, aged 20-57 years (mean 36 years). All of the patients underwent PET-CT scanning before surgery, and the resected specimens were postoperatively classified according to preoperative PET-CT. The resected specimens were divided into areas with increased fluorodeoxyglucose (FDG) metabolism (SUVmax>3) and areas with normal FDG metabolism (SUVmax ≤ 3) according to the preoperative PET-CT performance. After sample processing, total RNA was extracted from the tissues of different regions, and then whole gene transcriptome sequencing was performed. Bioinformatics analysis of the two sets of data was performed to discover the expression profiles of the differences in whole gene transcriptome data between the two regions and to screen for candidate biomarkers. Eighty patients with sputum-negative pulmonary tuberculosis admitted to Shanghai Public Health Clinical Center from January 1, 2019 to January 1, 2021 were retrospectively collected as the validation group, including 37 males and 43 females, aged 20-62 years, with an average age of 39 years. The validation group was divided into a group with increased SUV (n=40) and a group without lesions on CT imaging (n=40). Enzyme-linked immunosorbent assay (ELISA) was used to determine the protein levels of candidate biomarkers in the peripheral plasma of patients. The effect of biomarkers was assessed using subject operating characteristic (ROC) curves. Student's t-test was used to determine whether the difference in protein levels between the two groups was statistically significant. Results: Bioinformatics analysis revealed that the expression levels of C1QB, CCL19, CCL5 and HLA-DMB correlated with the metabolic activity of sputum-negative tuberculosis lesion tissue. Further screening and validation by the validation group confirmed that the difference in C1QB protein levels in the peripheral plasma of patients was statistically significant between the group with increased SUV and the group without lesions on CT imaging [(3.55±0.34) mg/L vs. (2.75±0.21) mg/L, t=4.12, P<0.001]. And the ROC curve showed that the area under the curve for C1QB protein levels was 0.731, which had potential clinical value. Conclusion: The C1QB protein level can be used to assess the activity of lesions in patients with sputum-negative tuberculosis and is a potential biomarker.

Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. METHODS: A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. RESULTS: In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. CONCLUSIONS: Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

Hollow-Core-Photonic-Crystal-Fiber-Based Miniaturized Sensor for the Detection of Aggregation-Induced-Emission Molecules.

A miniature sensor for detection of aggregation-induced-emission (AIE) molecules is proposed in this work. The sensing head is fabricated by use of hollow-core photonic crystal fiber with a core diameter of about 4.8 µm. The cladding holes are sealed with a fusion splicing technique, and the central hole remains open to allow the filtration of solution with AIE molecules. When the solution is excited by an ultraviolet lamp, the fluorescence is received by a fiber-optic spectrometer. The fluorescence intensity is associated with the concentration of AIE molecules and the infiltrated-core length. In the whole process of the experiments, the output-peak wavelength is stable, which indicates that the existing forms of AIE particles are stable, and the fluorescence reabsorption can be neglected. The experimental results obtained are in accordance with traditional microplate-spectrophotometer methods. The most exciting result is that the amount of sample measured can be as low as 0.36 nL, which allows the detection of AIE molecules at only 0.02 pmol. In addition, the miniature sensor was successfully applied to the detection of an AIE-based bioprobe for evaluating the activity of the dipeptidyl-peptidase 4 (DPP-4) inhibitor sitagliptin with an IC50 of 59.80 ± 3.06 nM. The advantages of small device size and nanoliter-scale sample volumes suggest that the proposed sensor is promising for many biosensing applications.

[Children's non-carcinogenic health risk assessment of heavy metals exposure to residential indoor dust around an e-waste dismantling area in South China].

Objective: To evaluate the non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) in residential indoor dust for young children around an e-waste dismantling area in South China. Methods: A village around an e-waste dismantling area in South China was selected as a research site in October 2016. Convenience sampling method was used to select 36 houses in the village and 36 dust samples were collected by vacuum cleaner. The concentrations of heavy metals (Cd, Cr, Cu, Mn, Pb and Zn) in each sample were determined and expressed by the average value. Non-carcinogenic health risk assessment was conducted using the US Environmental Protection Agency (EPA) Health Risk Assessment (HRA) model, the American Toxicology and Disease Registry (ATSDR) Target-organ Toxicity Dose (TTD) approach and the ATSDR Binary Weight-of-Evidence (BINWOE) model. Results: The mean ± SD of concentrations of As, Cd, Cr, Cu, Mn, Pb and Zn were (48.90±33.91), (5.95±3.89), (173.57±580.37), (412.71±1 190.00), (612.82±540.70), (297.41±293.22) and (1 052.81±1 156.48) mg/kg, respectively. The HI value of TTD (2.670) and BINWOE (2.933) were higher than the safety threshold of EPA recommended non-carcinogenic health risk. The HI value of TTD and BINWOE were 1.93 and 2.12 times higher than the HI value of HRA (1.386). Conclusion: There was non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) via residential indoor dust around the e-waste dismantling area for local children.

[Safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms in dementia: a meta-analysis].

Objective: To assess the safety of olanzapine, risperidone and quetiapine drugs in dementia patients with behavioral and psychological symptoms. Methods: The EMBASE, Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews, Medline, CNKI, Wang Fang were systematically searched for eligible randomized controlled trials of olanzapine, risperidone and quetiapine drugs therapy in patients with psychotic symptoms of dementia before February 2016. Two reviewers independently assessed the quality of the trials and extracted information. All the data was analyzed with meta analysis and software of the Revman5.3 provided by Cochrane network. Results: Overall, 16 relevant RCTs with 1 727 participants were identified (olanzapine group: 672; quetiapine group: 395; risperidone group: 660). (1)Olanzapine group had higher incidence of somnolence than risperidone group (OR=1.49, 95% CI [-1.01-2.21], P=0.05), while for the dizziness, agitation, accidental injury, weight gain, abnormal gait, weakness, sleep disorders, extrapyramidal symptoms, there were no significant difference. (2) Risperidone had higher incidence of extrapyramidal symptoms than quetiapine group (OR=0.11, 95% CI [0.04-0.27], P=0.64), the incidence of somnolence was lower than quetiapine group (OR=0.03, 95% CI [1.06-3.51], P=0.03), while for accidental injury, dizziness, fatigue, insomnia, constipation, there were no significant difference. (3) Olanzapine group had higher incidence of extrapyramidal symptoms than quetiapine group (OR=11.10, 95% CI [3.35-36.75], P<0.000 1), while for somnolence, sleep disturbances, constipation, agitation, weight gain, dizziness, there was no significant difference. (4) The subgroup analysis showed that in the Chinese population, compared with the population in Europe and America, risperidone group had higher incidence of agitation, sleep disorders than olanzapine (agitation: [OR= 0.26, 95% CI [0.08-0.82]; sleep disorders: OR= 0.31, 95% CI [0.10-0.99]), olanzapine group had higher incidence of weight gain than quetiapine (OR=6.8, 95% CI [2.00-23.14]). Conclusions: Among olanzapine, risperidone and quetiapine, risperidone has lowest incidence of somnolence, quetiapine has lowest incidence of extrapyramidal symptoms. In the Chinese population, compared with the population in Europe and America, risperidone group has higher incidence of agitation, sleep disorders than olanzapine, and olanzapine group has higher incidence of weight gain than quetiapine.

[Application of Chinese version of ACE-â ¢ in type 2 diabetes mellitus patients with mild cognitive impairment].

Objective: To investigate the application and best cut-off value of Chinese version of Addenbrooke's cognitive examination-Ⅲ(ACE-Ⅲ) in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment. Methods: A total of 18 T2DM patients with normal cognitive function (NCI group) and 40 T2DM patients with mild cognitive impairment (MCI group) treated in outpatient clinic or ward of Department of Neurology and Endocrinology in Fujian Medical University Union Hospital between January 2015 and February 2016 were enrolled. Mini Mental State Scale (MMSE), Montreal cognitive assessment scale (MoCA), Activity of Daily Living Scale (ADL) and the Chinese version of ACE-Ⅲ were used to assess cognitive function of subjects and to assess the value of ACE-Ⅲ in the diagnosis of T2DM patients with mild cognitive impairment. Results: The Cronbach's alpha of the Chinese version of ACE-Ⅲ is 0.768. ACE-Ⅲ and MoCA were correlative (r=0.768, P<0.001). The area under the receiver operating characteristic (ROC) curve for ACE-Ⅲ was 0.906 (95%CI: 0.827-0.985). When the cut-off value for diagnosis was 87.5, the maximum Youden index was 0.769, with a sensitivity of 0.825 and a specificity of 0.944. Patients in MCI group got a lower score in the sub-items of attention/orientation, memory, verbal fluency, language and visual space of ACE-Ⅲ compared to those in NCI group, and the differences were statistically significant (t=5.336, P<0.001; t=5.530, P<0.001; t=4.556, P<0.001; t=5.301, P<0.001; t=2.821, P=0.008). Conclusion: The Chinese version of ACE-Ⅲ had good internal consistency reliability, and it could effectively detect impairment of general cognitive function and single cognitive domains in T2DM patients.

HLA-B*13:01 and the dapsone hypersensitivity syndrome.

BACKGROUND: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. METHODS: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. RESULTS: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. CONCLUSIONS: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

Identification of the Lowest T=2, J

Masses of ^{52g,52m}Co were measured for the first time with an accuracy of ∼10 keV, an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous ß-γ measurements of ^{52}Ni, the T=2, J^{π}=0^{+} isobaric analog state (IAS) in ^{52}Co was newly assigned, questioning the conventional identification of IASs from the ß-delayed proton emissions. Using our energy of the IAS in ^{52}Co, the masses of the T=2 multiplet fit well into the isobaric multiplet mass equation. We find that the IAS in ^{52}Co decays predominantly via γ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS.

Sunitinib modulates the radiosensitivity of esophageal squamous cell carcinoma cells in vitro.

This study aims to explore the radiosensitivity of sunitinib on esophageal cancer cell lines. For in vitro studies, human esophageal squamous cell carcinoma (ESCC) cell lines were treated with sunitinib 24 hours before irradiation. ESCC cell lines were treated with sunitinib with or without radiation. Cell proliferation was detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis and cell cycle analysis were detected by flow cytometry. Deoxyribonucleic acid (DNA) double-strand breaks were performed by immunocytofluorescence analysis. Western blot analysis was used to determine the effect of sunitinib on radiation induced signal transduction. Sunitinib potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.13-1.72. Furthermore, sunitinib increased radiation induced DNA double-strand breaks, promoted the apoptosis of ESCC cells and induced the G2/M arrest. Radiosensitization was accompanied with enhanced apoptosis and regulated by the intrinsic pathway of apoptosis. Sunitinib sensitized ESCC cells to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in esophageal cancer.

In vitro expansion and differentiation of rat pancreatic duct-derived stem cells into insulin secreting cells using a dynamicthree-dimensional cell culture system.

In this study, a dynamic three-dimensional cell culture technology was used to expand and differentiate rat pancreatic duct-derived stem cells (PDSCs) into islet-like cell clusters that can secrete insulin. PDSCs were isolated from rat pancreatic tissues by in situ collagenase digestion and density gradient centrifugation. Using a dynamic three-dimensional culture technique, the cells were expanded and differentiated into functional islet-like cell clusters, which were characterized by morphological and phenotype analyses. After maintaining 1 x 108 isolated rat PDSCs in a dynamic three-dimensional cell culture for 7 days, 1.5 x 109 cells could be harvested. Passaged PDSCs expressed markers of pancreatic endocrine progenitors, including CD29 (86.17%), CD73 (90.73%), CD90 (84.13%), CD105 (78.28%), and Pdx-1. Following 14 additional days of culture in serum-free medium with nicotinamide, keratinocyte growth factor (KGF), and b fibroblast growth factor (FGF), the cells were differentiated into islet-like cell clusters (ICCs). The ICC morphology reflected that of fused cell clusters. During the late stage of differentiation, representative clusters were non-adherent and expressed insulin indicated by dithizone (DTZ)-positive staining. Insulin was detected in the extracellular fluid and cytoplasm of ICCs after 14 days of differentiation. Additionally, insulin levels were significantly higher at this time compared with the levels exhibited by PDSCs before differentiation (P < 0.01). By using a dynamic three-dimensional cell culture system, PDSCs can be expanded in vitro and can differentiate into functional islet-like cell clusters.

[Current status regarding the cardiovascular disease-related risk levels among the hypertensive population of different ethnicities in Xinjiang Uygur Autonomous Region, China].

OBJECTIVE: To assess the status of the cardiovascular disease associated risk levels among hypertensive population of Han, Uygur and Kazakh ethnicities, in Xinjiang Uygur Autonornous Region, to guide hypertension prevention and treatment in different ethnicities. METHODS: Four stages random cluster sampling method was used, and all the data was collected from Xinjiang local residents aged over 18 between October 2007 and March 2010. RESULTS: A total of 14 618 subjects completed this survey, in which 2 654 Han, 1 612 Uygur and 2034 Kazakh people diagnosed with hypertension was included in this research. Most of them were"grade 1 hypertension", and the percentage of grade 3 hypertension was Han (19.1%), Uygur (17.3%) and Kazakh (32.3%), respectively. Majority hypertensive people accompanied with 1 risk factor. The risk proportions of low, medium, high and very high in hypertension population of different ethnicities were Han (19.4%, 34.6%, 46.1%), Uygur (17.7%, 37.6%, 44.7%), Kazakh (12.5%, 38.0%, 49.4%) respectively. In Han, Uygur and Kazakh ethnicities, the percentage of high risk and very high risk was highest in hypertensive men aged over 60 years old.The percentages of hypertension awareness were 42.0%, 45.6%, 46.5% and percentages of medicine therapy were 29.6%, 23.4%, 25.2% for Han, Uygur and Kazakh ethnicities, respectively. CONCLUSIONS: Hypertensive people among Han, Uygur and Kazakh ethnicities in Xinjiang are mainly under high risk and very high risk situation of cardiovascular disease, especially in men aged ≥60. The percentage of hypertension awareness and medicine therapy in high risk and very high risk population is the highest, while percentage of awareness in medium risk population is low.

Spectral measurement of electron antineutrino oscillation amplitude and frequency at Daya Bay.

A measurement of the energy dependence of antineutrino disappearance at the Daya Bay reactor neutrino experiment is reported. Electron antineutrinos (ν¯(e)) from six 2.9 GW(th) reactors were detected with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls. Using 217 days of data, 41 589 (203 809 and 92 912) antineutrino candidates were detected in the far hall (near halls). An improved measurement of the oscillation amplitude sin(2)2θ(13)=0.090(-0.009)(+0.008) and the first direct measurement of the ν¯(e) mass-squared difference |Δm(ee)2|=(2.59(-0.20)(+0.19))×10(-3) eV2 is obtained using the observed ν¯(e) rates and energy spectra in a three-neutrino framework. This value of |Δm(ee)2| is consistent with |Δm(µµ)2| measured by muon neutrino disappearance, supporting the three-flavor oscillation model.

Effects of different dietary vitamin D combinations during the grower phase and the feed restriction phase on growth performance and sternal morphology, mineralization, and related genes expression of bone metabolism in Pekin ducks.

Our study aimed to investigate the effects of different dietary vitamin D (VD) combinations during the grower (1-32 d of age) and feed restriction (33-52 d of age) phases on growth performance. We also evaluated sternal morphology, mineralization, and related genes expression of bone metabolism as well as absorption of calcium and phosphorous in duodenal mucosa and kidney in Pekin ducks. During the grower phase, we used 2 VD regimes (Group A: 3,160 IU/kg VD3; Group B: 400 IU/kg VD3 + 69 µg/kg 25-OH-D3). Each dietary treatment had 50 replicate pens of 10 ducks per pen. During the feed restriction phase, 30 replicate pens selected from Group A and Group B, repetitively, were redivided into 5 different dietary VD regimes to form a 2 × 5 experimental design. Each group consisted of 6 replicates, each with 10 ducks. During the feed restriction phase, we evaluated 5 different dietary VD combinations were as follows: T1: 2,000 IU/kg VD3 ; T2: 5,000 IU/kg VD3; T3: 3,620 IU/kg VD3 + 34.5 µg/kg 25-OH-D3; T4: 2,240 IU/kg VD3 + 69 µg/kg 25-OH-D3; T5: 1,800 IU/kg VD3 + 80 µg/kg 25-OH-D3). Results showed that Group B combinations with T5 had a better growth performance and breast meat deposition (P < 0.1). Regardless of 5 dietary VD regimes during the feed restriction phase, Group B significantly increased (P < 0.05) 52 d sternal depth and tended to increase (P < 0.1) 52 d sternal defatted weight, ash content, and phosphate (P) content of ducks. A significant interactive effect (P < 0.05) was observed on the mRNA abundance of DMP1 and Sost1 as well as RANKL/OPG in sternum and of VDR in duodenal mucosa of ducks at 52 d of age between dietary VD combinations during 2 phases. These results indicated that dietary VD regimes during the grower phase could affect the effectiveness of dietary VD regimes during the feed restriction phases; Dietary VD combinations of both phases could affect the genes expression of bone formation and the absorption as well as reabsorption of calcium and phosphorus in duodenum and kidney.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.