Cell-type differential targeting of SETDB1 prevents aberrant CTCF binding, chromatin looping, and cis-regulatory interactions.

SETDB1 is an essential histone methyltransferase that deposits histone H3 lysine 9 trimethylation (H3K9me3) to transcriptionally repress genes and repetitive elements. The function of differential H3K9me3 enrichment between cell-types remains unclear. Here, we demonstrate mutual exclusivity of H3K9me3 and CTCF across mouse tissues from different developmental timepoints. We analyze SETDB1 depleted cells and discover that H3K9me3 prevents aberrant CTCF binding independently of DNA methylation and H3K9me2. Such sites are enriched with SINE B2 retrotransposons. Moreover, analysis of higher-order genome architecture reveals that large chromatin structures including topologically associated domains and subnuclear compartments, remain intact in SETDB1 depleted cells. However, chromatin loops and local 3D interactions are disrupted, leading to transcriptional changes by modifying pre-existing chromatin landscapes. Specific genes with altered expression show differential interactions with dysregulated cis-regulatory elements. Collectively, we find that cell-type specific targets of SETDB1 maintain cellular identities by modulating CTCF binding, which shape nuclear architecture and transcriptomic networks.

Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal-fetal interface following SARS-CoV-2 infection.

During pregnancy the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.

Initial characterization of gap phase introduction in every cell cycle of C. elegans embryogenesis.

Early embryonic cell cycles usually alternate between S and M phases without any gap phase. When the gap phases are developmentally introduced in various cell types remains poorly defined especially during embryogenesis. To establish the cell-specific introduction of gap phases in embryo, we generate multiple fluorescence ubiquitin cell cycle indicators (FUCCI) in C. elegans. Time-lapse 3D imaging followed by lineal expression profiling reveals sharp and differential accumulation of the FUCCI reporters, allowing the systematic demarcation of cell cycle phases throughout embryogenesis. Accumulation of the reporters reliably identifies both G1 and G2 phases only in two embryonic cells with an extended cell cycle length, suggesting that the remaining cells divide either without a G1 phase, or with a brief G1 phase that is too short to be picked up by our reporters. In summary, we provide an initial picture of gap phase introduction in a metazoan embryo. The newly developed FUCCI reporters pave the way for further characterization of developmental control of cell cycle progression.

Genomic architecture of 5S rDNA cluster and its variations within and between species.

BACKGROUND: Ribosomal DNAs (rDNAs) are arranged in purely tandem repeats, preventing them from being reliably assembled onto chromosomes during generation of genome assembly. The uncertainty of rDNA genomic structure presents a significant barrier for studying their function and evolution. RESULTS: Here we generate ultra-long Oxford Nanopore Technologies (ONT) and short NGS reads to delineate the architecture and variation of the 5S rDNA cluster in the different strains of C. elegans and C. briggsae. We classify the individual rDNA's repeating units into 25 types based on the unique sequence variations in each unit of C. elegans (N2). We next perform assembly of the cluster by taking advantage of the long reads that carry these units, which led to an assembly of 5S rDNA cluster consisting of up to 167 consecutive 5S rDNA units in the N2 strain. The ordering and copy number of various rDNA units are consistent with the separation time between strains. Surprisingly, we observed a drastically reduced level of variation in the unit composition in the 5S rDNA cluster in the C. elegans CB4856 and C. briggsae AF16 strains than in the C. elegans N2 strain, suggesting that N2, a widely used reference strain, is likely to be defective in maintaining the 5S rDNA cluster stability compared with other wild isolates of C. elegans or C. briggsae. CONCLUSIONS: The results demonstrate that Nanopore DNA sequencing reads are capable of generating assembly of highly repetitive sequences, and rDNA units are highly dynamic both within and between population(s) of the same species in terms of sequence and copy number. The detailed structure and variation of the 5S rDNA units within the rDNA cluster pave the way for functional and evolutionary studies.

Computable early Caenorhabditis elegans embryo with a phase field model.

Morphogenesis is a precise and robust dynamic process during metazoan embryogenesis, consisting of both cell proliferation and cell migration. Despite the fact that much is known about specific regulations at molecular level, how cell proliferation and migration together drive the morphogenesis at cellular and organismic levels is not well understood. Using Caenorhabditis elegans as the model animal, we present a phase field model to compute early embryonic morphogenesis within a confined eggshell. With physical information about cell division obtained from three-dimensional time-lapse cellular imaging experiments, the model can precisely reproduce the early morphogenesis process as seen in vivo, including time evolution of location and morphology of each cell. Furthermore, the model can be used to reveal key cell-cell attractions critical to the development of C. elegans embryo. Our work demonstrates how genetic programming and physical forces collaborate to drive morphogenesis and provides a predictive model to decipher the underlying mechanism.

Value of contrast-enhanced ultrasound quantitative analysis combined with ACR TI-RADS classification in the differential diagnosis of thyroid solid nodules / 中华超声影像学杂志

Objective:To evaluate the value of VueBox ? contrast-enhanced ultrasound (CEUS) quantitative analysis combined with ACR TI-RADS classification in the diagnosis of benign and malignant solid thyroid nodules. Methods:A total of 201 patients with thyroid solid nodules (201 nodules) who underwent surgery or puncture biopsy in the People′s Hospital of Guangxi Zhuang Autonomous Region were enrolled from October 2020 to February 2022. The preoperative conventional ultrasound and contrast-enhanced ultrasound images were retrospectively analyzed. According to the pathological results, they were divided into the malignant group and benign group. The differences of the quantitative parameters of CEUS between the two groups were analyzed, including peak enhancement (PE), wash-in and wash-out area under the curve (WiWoAUC), wash-in perfusion index (WiPI). ΔPE, ΔWiWoAUC, ΔWiPI were obtained by calculating the parameter difference between the surrounding normal glands and nodules. ROC curve was used to analyze the value of different quantitative parameters in the differential diagnosis of benign and malignant solid thyroid nodules. The CEUS quantitative parameters with best diagnostic performance was selected and combined with ACR TI-RADS classification system to evaluate the diagnostic efficiency of the single diagnostic approaches and the combined approach.Results:The quantitative parameters of PE, WiWoAUC, WiPI, ΔPE, ΔWiWoAUC, ΔWiPI were significantly different between benign group and malignant group (all P<0.001). ΔPE had the highest diagnostic value among all the quantitative parameters (the area under the ROC curve was 0.802), and the cut-off value was 0.21.ΔPE combined with ACR TI-RADS classification showed the best efficiency in diagnosis of benign and malignant thyroid nodules, with an area under the curve of 0.898, and the sensitivity, specificity, positive predictive value and negative predictive value of 73.39%, 93.48%, 93.02% and 74.78%, respectively. Conclusions:Quantitative parameters of CEUS by using VueBox ? software is valuable for the differential diagnosis of benign and malignant solid thyroid nodules, and its combination with ACR TI-RADS classification can improve the diagnosis accuracy.

Establishment of a morphological atlas of the Caenorhabditis elegans embryo using deep-learning-based 4D segmentation.

The invariant development and transparent body of the nematode Caenorhabditis elegans enables complete delineation of cell lineages throughout development. Despite extensive studies of cell division, cell migration and cell fate differentiation, cell morphology during development has not yet been systematically characterized in any metazoan, including C. elegans. This knowledge gap substantially hampers many studies in both developmental and cell biology. Here we report an automatic pipeline, CShaper, which combines automated segmentation of fluorescently labeled membranes with automated cell lineage tracing. We apply this pipeline to quantify morphological parameters of densely packed cells in 17 developing C. elegans embryos. Consequently, we generate a time-lapse 3D atlas of cell morphology for the C. elegans embryo from the 4- to 350-cell stages, including cell shape, volume, surface area, migration, nucleus position and cell-cell contact with resolved cell identities. We anticipate that CShaper and the morphological atlas will stimulate and enhance further studies in the fields of developmental biology, cell biology and biomechanics.

Transmission Dynamics of Coronavirus Disease 2019 (COVID-19) in the World: The Roles of Intervention and Seasonality

The coronavirus disease 2019 (COVID-19) is spreading rapidly all over the world. The transmission dynamics of the COVID-19 pandemic is still unclear, but developing strategies for mitigating the severity of the pandemic is yet a top priority for global public health. In this study, we developed a novel compartmental model, SEIR-CV(susceptible-exposed-infectious-removed with control variables), which not only considers the key characteristics of asymptomatic infection and the effects of seasonal variations, but also incorporates different control measures for multiple transmission routes, so as to accurately predict and effectively control the spread of COVID-19. Based on SEIR-CV, we predicted the COVID-19 epidemic situation in China out of Hubei province and proposed corresponding control strategies. The results showed that the prediction results are highly consistent with the outbreak surveillance data, which proved that the proposed control strategies have achieved sound consequent in the actual epidemic control. Subsequently, we have conducted a rolling prediction for the United States, Brazil, India, five European countries (the United Kingdom, Italy, Spain, Germany, and France), southern hemisphere, northern hemisphere, and the world out of China. The results indicate that control measures and seasonal variations have a great impact on the progress of the COVID-19 pandemic. Our prediction results show that the COVID-19 pandemic is developing more rapidly due to the impact of the cold season in the southern hemisphere countries such as Brazil. While the development of the pandemic should have gradually weakened in the northern hemisphere countries with the arrival of the warm season, instead of still developing rapidly due to the relative loose control measures such as the United States and India. Furthermore, the prediction results illustrate that if keeping the current control measures in the main COVID-19 epidemic countries, the pandemic will not be contained and the situation may eventually turn to group immunization, which would lead to the extremely severe disaster of about 5 billion infections and 300 million deaths globally. However, if Chinas super stringent control measures were implemented from 15 July, 15 August or 15 September 2020, the total infections would be contained about 15 million, 32 million or 370 million respectively, which indicates that the stringent and timely control measures is critical, and the best window period is before September for eventually overcoming COVID-19. SignificanceCOVID-19 is now posing a huge threat to global public health. The key features such as asymptomatic infection and droplet or airborne transmission make COVID-19 more easily spread and more widely distributed around the world. It is an urgent need to explore the optimal intervention strategies and measures to contain the pandemic. Our novel SEIR-CV compartmental model considers the new features of COVID-19, exhibits the impact of the intervention strategies and seasonal variations, and thus can accurately predicts its trajectory in China and the rest of the world. Our research results suggest that control measures and seasonal variations have a great impact on the development of the COVID-19 pandemic, which can only be contained by stringent strategies during the best window period before September 2020 for eventually overcoming COVID-19, otherwise it would cause a severer global catastrophe.

Establishment of Signaling Interactions with Cellular Resolution for Every Cell Cycle of Embryogenesis.

Intercellular signaling interactions play a key role in breaking fate symmetry during animal development. Identification of signaling interactions at cellular resolution is technically challenging, especially in a developing embryo. Here, we develop a platform that allows automated inference and validation of signaling interactions for every cell cycle of Caenorhabditis elegans embryogenesis. This is achieved by the generation of a systems-level cell contact map, which consists of 1114 highly confident intercellular contacts, by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of the Notch signaling pathway with cellular resolution using the automated expression profiling technique, we are able to refine existing and identify novel Notch interactions during C. elegans embryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions during cell division in breaking fate symmetry. Finally, we describe the development of a website that allows online access to the cell-cell contact map for mapping of other signaling interactions by the community. The platform can be adapted to establish cellular interactions from any other signaling pathway.

Evaluating patients' perception of service quality at hospitals in nine Chinese cities by use of the ServQual scale

Objective: To investigate patients' perception of service quality at hospitals in nine Chinese cities and propose some measures for improvement. Methods: The ServQual scale method was used in a survey involving patients at outpatient and in-patient facilities in Shanghai, Chongqing, Chengdu, Nanning, Guilin and Laibin of Guangxi, Honghezhou of Yunnan, Wulumuqi of Xinjiang and Zhongshan of Guangdong. The data collected were entered and analyzed using SPSS 20.0. Statistical analyses included descriptive statistics, factor analyses, reliability analyses, productmoment correlations, independent-sample t-tests, One-way ANOVA and regression analyses. Results: The Kaiser-Meyer-Olkin value for the factor analysis of the scale was 0.979. The Cronbach's α for the reliability analysis was 0.978. All the Pearson correlation coefficients were positive and statistically significant. Visitors to out-patient facilities reported more positive perception than visitors to in-patient facilities on tangibles (t = 4.168, P < 0.001) and reliability (t = 1.979, P < 0.05). Patients of 60 years of age and above reported more positive perception than those between 40 and 49 on reliability (F = 3.311, P = 0.010), assurances (F = 2.751, P < 0.05) and empathy (F = 4.009, P = 0.003). For the five dimensions of the scale, patients in Laibin, Guangxi reported the most positive perceived service quality, followed by patients in Shanghai. On the other hand, patients in Chongqing and Nanning and Guilin of Guangxi reported relatively poor perceptions of service quality. Standardized regression coefficients showed statistically significant (P < 0.001) positive values for all ServQual dimensions. Empathy (β = 0.267) and reliability (β = 0.239) most strongly predicted perception of service quality. Conclusions: Chinese patients perceived service quality as satisfactory. Hospitals in various regions of China should enhance their awareness and ability to serve their patients.

Association between sleep quality and body mass index among Chinese nonagenarians/centenarians.

We examined the individual association between body mass index (BMI) and sleep quality among the very elderly. The present study analyzed data from survey that was conducted on all residents aged 90 years or more in a district, there were 2,311,709 inhabitants in 2005. Subjects were divided into four groups according to quartile of BMI (<16.6, 16.6-18.9, 18.9-21.1, >21.1 kg/m(2)) and according to classification criteria of underweight, normal weight, overweight, and obesity in BMI (<18.5, 18.5-23.0, 23.0-27.5, >27.5 kg/m(2)), respectively. Sleep quality was measured using The Pittsburgh Sleep Quality Index (PSQI). Sleep quality included quality classification and scores, sleep duration, sleep latency, and sleep efficiency. The subjects included in the statistical analysis were 216 men and 444 women. According to quartile of BMI or classification criteria of underweight, normal weight, overweight, and obesity in BMI, none of the differences in sleep quality scores, sleep latency, sleep duration, sleep efficiency percentage, and prevalence of poor sleep quality was significant among different BMI groups. The difference in BMI between subjects with good and poor sleep quality was non-significant. Unadjusted and adjusted multiple logistic regression showed that none of the BMI groups had a function of decreasing the risk for poor quality. Among longevity Chinese, there is no association between BMI and sleep quality.

Gastroprotective activities of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) on the growth of the stomach cancer AGS cell line and indomethacin-induced gastric ulcers.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) seeds have long been used to treat warts, chapped skin, rheumatism, and neuralgia in traditional Chinese medicine (TCM). Recently, studies demonstrated its anti-inflammatory, antiproliferative, antitumor, and antiallergic activities. In the present study, we first report the gastroprotective effects of dehulled adlay (DA) seeds, which consist of bran (AB) and endosperm (AE). The DA ethanolic extract (DAE) was prepared, along with the AB and AE ethanolic extracts (ABE and AEE), and the inhibitory effects of these extracts were tested on the AGS gastric cancer cell line. Results indicated that the ABE showed better antiproliferative activity, and 19 compounds were purified from AB in a further phenolic-compound-guided separation. Among the isolated compounds, caffeic and chlorogenic acids significantly suppressed the growth of AGS cells. In addition, the antiulcer activity of DA was examined in an indomethacin-induced gastric lesion model. The ulcer index (UI) and oxidative biomarkers in animals decreased, while the non-protein sulfhydryl (NPSH) groups were elevated when given DA. This is the first investigation of antiulcer activity of adlay, and we demonstrated that the antioxidative-active phenolic acids in DA contribute to some portion of the gastroprotective effects.

Cost-utility analysis of Parkinson's disease.

Many expensive treatments have been developed for Parkinson's disease (PD), and a good cost-utility analysis is required. Quality-adjusted life-years (QALY) allows comparison of the cost-utility of different medical conditions. If a treatment strategy gives a patient an extra but unhealthy year, the QALY he obtained will be less than one. When a therapeutic strategy is more effective, but causes higher costs, it is mandatory to calculate the incremental cost-effectiveness ratio (ICER). In keeping with guidance from the UK National Institute for Health and Clinical Excellence (NICE), a therapy that deliver QALYs of £20,000 or less are likely to be approved. The threshold used by NICE for the maximum it is prepared to pay for a QALY, which lies between £20,000 and £30,000, will be reviewed case by case. Subthalamic deep brain stimulation (STN-DBS) is an effective therapy, which can improve the quality of life in PD patients immediately, but has not been approved by the Bureau of National Health Insurance here. It has been estimated that the ICER/QALY in STN-DBS patients was of 34,389C= , which is within appropriate limits to consider STNDBS as an efficient therapy. We expect that we can have a decision-making mechanism similar to that of NICE that, according to the ICER of each medical condition, medical resource can be redistributed openly and justly.

Clinicopathologic correlation between CD4-positive T lymphocyte counts and superficial lymphadenopathy in HIV-positive/AIDS patients / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological correlation between CD4(+) T lymphocyte count and superficial lymphadenopathy HIV/AIDS patients.</p><p><b>METHODS</b>A total of 1066 HIV/AIDS patients were included in this study. The incidence of superficial lymphadenopathy, peripheral blood CD4(+) T lymphocyte counts and histological features of superficial lymphadenopathy were analyzed.</p><p><b>RESULTS</b>Among 1066 patients, 126 cases (11.8%) presented with superficial lymphadenopathy. Of the 126 cases, there were 69 cases with CD4(+) T lymphocyte counts < 100/µl and clinical diagnoses including tuberculosis (37 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy (18 cases), penicillium diseases (12 cases), fungal infection (5 cases) and non-tuberculous mycobacterial infection (1 case). Twenty-six cases had CD4(+) T lymphocyte counts between 100/µl to 200/µl and clinical diagnosis including tuberculosis (12 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy(6 cases), penicillium disease (2 cases) and non-Hodgkin lymphoma (1 case). Twenty-nine cases had CD4(+) T lymphocyte counts > 200/µl and clinical diagnoses including tuberculosis (11 cases), reactive hyperplasia (12 cases), AIDS-related lymphadenopathy (3 cases), Penicillium diseases (1 case) and non-Hodgkin lymphoma (4 cases). The CD4(+) T lymphocyte counts among patients with tuberculosis, AIDS-related lymphadenopathy and Penicillium diseases were significantly different (χ(2) = 8.861, P = 0.012). A significant correlation between the incidence of superficial lymphadenopathy and CD4(+) T lymphocyte counts was found (χ(2) = 375.41, P = 0.000).</p><p><b>CONCLUSIONS</b>The most common cause of superficial lymphadenopathy in HIV/AIDS patients is tuberculosis, followed by lymph node reactive hyperplasia, AIDS-related lymphadenopathy and Penicillium disease. Low CD4(+) T lymphocyte count correlates with an increased incidence of superficial lymphadenopathy and the risk of opportunity infection. Therefore, determination of peripheral blood CD4(+) T lymphocyte count should become an integral marker for the early diagnosis and treatment of superficial lymphadenopathy in HIV/AIDS patients.</p>

Depression and hypertension among Chinese nonagenarians and centenarians.

PURPOSE: In this study, we explored association between hypertension and depression in the very elderly using a sample ranged in age from 90 to 108 years. METHODS: A cross-sectional study. RESULTS: The sample included 687 unrelated Chinese nonagenarians/centenarians (67.4% women, mean age 93.51 years). The mean depression score (measured with brief 23-item geriatrics depression scale Chinese-edition (GDS-CD)) was 8.46 (standard deviation (SD) 3.33 range 0-20). There was no significant difference in depression scores between subjects with and without hypertension and there was also no significant difference in depression prevalence between subjects with and without hypertension. There was no significant difference in prevalence of hypertension between subjects with and without depression and there were also no significant differences in levels of arterial blood pressure (including SBP and DBP). Neither odd ratio (OR) of depression as a function of increased hypertension nor OR of hypertension as a function of increased depression was significant. CONCLUSIONS: In summary, we found that depression was not directly correlated with hypertension among Chinese nonagenarians and centenarians.

Health status and risk for depression among the elderly: a meta-analysis of published literature.

OBJECTIVE: the goal of this study was to determine the relationship between health status, including self-rated health status and chronic disease, and risk for depression among the elderly. METHOD: MEDLINE, EMBASE and The Cochrane Library Database were used to identify potential studies. The studies were classified into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study) or incident cases (for longitudinal study) of depression in each health status group were extracted and entered into Review Manager 4.2. The quantitative meta-analysis of cross-sectional studies and that of longitudinal studies were performed, respectively. For prevalence and incidence rates of depression, odds risk and relative risk (RR) were calculated, respectively. RESULTS: the quantitative meta-analysis showed that, compared with the elderly without chronic disease, those with chronic disease had higher risk for depression (RR: 1.53, 95% confidence intervals (CI): 1.20-1.97). Compared with the elderly with good self-rated health, those with poor self-rated health had higher risk for depression (RR: 2.40, 95% CI: 1.94-2.97). CONCLUSIONS: despite the methodological limitations of this meta-analysis, both poor self-rated health status and the presence of chronic disease are risk factors for depression among the elderly. In the elderly, poor self-reported health status appears to be more strongly associated with depression than the presence of chronic disease.

Pro12Ala polymorphism in PPARgamma2 associated with depression in Chinese nonagenarians/centenarians.

BACKGROUND AND AIMS: The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARgamma) has been associated with decreased obesity, insulin resistance, type 2 diabetes and other age-associated diseases such as cognitive impairment, hypertension, cancer, osteoarthritis. Each one of these diseases had been linked to depression. Moreover, there is also an association between Pro12 Ala polymorphism in PPAR gamma2 and longevity. The aim of the study was to evaluate the association between Pro12 Ala polymorphism and depression in Chinese nonagenarians and centenarians. METHODS: The sample included 697 unrelated Chinese nonagenarians/centenarians (aged between 90-108 years, mean age: 93.5+/-3.35 years; 67.2% women). The Pro12Ala variant was examined using polymerase chain reaction-restriction fragment length polymorphism. Depression was measured with brief 23-item Geriatrics Depression Scale Chinese-edition (GDS-CD). RESULTS: In this sample, the genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala, 9.2% Pro12Ala, 90.8% Pro12Pro and the prevalence of depression was 25.3%. Subjects who were 12Ala carriers had significantly lower prevalence of depression than those who were not 12Ala carriers (14.06 vs. 26.38%, p=0.034). Subjects without depression also had a higher frequency of 12Ala gene than those with depression (5.28 vs. 2.56%, p=0.031). Adjusting for certain clinical factors that may be associated with depression or with 12Ala carriers, multiple logistic regressions showed the 12Ala gene was associated with decreased incidence of depression. CONCLUSIONS: In summary, we found that among Chinese nonagenarians and centenarians, the Pro12Ala polymorphism in PPARgamma2 was associated with depression and that the 12Ala gene may be a factor for decreased depression.

Collaborative care interventions for depression in the elderly: a systematic review of randomized controlled trials.

OBJECTIVE: To determine the effective components and the feasibility of collaborative care interventions (CCIs) in the treatment of depression in older patients. METHODS: Systematic review of randomized controlled trials, in which CCIs were used to manage depression in patients aged 60 or older. RESULTS: We identified 3 randomized controlled trials involving 3930 participants, 2757 of whom received CCIs and the others received usual care. Collaborative care interventions were more effective in improving depression symptoms than usual care during each follow-up period. Compared with baseline, thoughts of suicide in subjects receiving CCIs significantly decreased (odds Ratio [OR], 0.52; 95% confidence intervals [CI], 0.35-0.77), but not that in those receiving usual care (OR, 0.85; 95% CI, 0.50-1.43). Subjects receiving CCIs were significantly more likely to report depression treatment (including any antidepressant medication and psychotherapy) than those receiving usual care during each follow-up period. Collaborative care interventions significantly increased depression-free days, but did not significantly increase outpatient cost. At 6 and 12 months postintervention, compared with those receiving usual care, participants receiving CCIs had lower levels of depression symptoms and thoughts of suicide. Moreover, participants receiving CCIs were significantly more likely to report antidepressant medication treatment, but were not significantly more likely to report psychotherapy. Collaborative care interventions with communication between primary care providers and mental health providers were no more effective in improving depression symptoms than CCIs without such communication. CONCLUSIONS: Collaborative care interventions are more effective for depression in older people than usual care and are also of high value. Antidepressant medication is a definitely effective component of CCIs, but communication between primary care providers and mental health providers seems not to be an effective component of CCIs. The effect of psychotherapy in CCIs should be further explored.

Insufficient renal 1-alpha hydroxylase and bone homeostasis in aged rats with insulin resistance or type 2 diabetes mellitus.

This study aimed to explore the relationship between insufficient renal 1-alpha hydroxylase (IRH) and bone homeostasis in type 2 diabetes mellitus (T2DM) or insulin resistance (IR) and to investigate whether IR plays a major role in the pathogenesis of both IRH and bone loss in T2DM. The experimental animal models of T2DM, IR, IR treated with vitamin D (VD), IR treated with 1-alpha hydroxyvitamin D (1alpha(OH) D, the product of renal 1-alpha hydroxylase), T2DM treated with VD, and T2DM treated with 1alpha(OH) D were established on 18-month-old male Wistar rats. For rats in each animal model and normal control rats, IR was detected by euglycemic insulin clamp technique (EICT) and glucose infusion rate (GIR, an index of IR) was calculated. Levels of serum 25-hydroxyvitamin D (25(OH)D) and serum active vitamin D (1,25(OH)(2)D) were determined by radioimmunoassay (RIA), and 1,25(OH)(2)D/25(OH)D ratio (1,25-25-R, an index of renal 1-alpha hydroxylase activity in vivo) was calculated; and bone mineral density (BMD) in femoral bone and lumbar vertebrae was measured by dual-energy X-ray absorption (DEXA). No significant difference was observed among the levels of 25(OH)D in all the rats. In IR rats, 1,25(OH)(2)D level, 1,25-25-R, and BMD level were significantly higher than those in T2DM rats and were lower than those in normal control rats. In the aged rats with T2DM or IR, administration of VD had no effect on 25(OH)D level, 1,25(OH)(2)D level, 1,25-25-R, and BMD level. Administration of 1alpha(OH) D had also no effect on 25(OH)D level but increased 1,25(OH)(2)D level, 1,25-25-R, and BMD level. For the aged rats with T2DM or IR, GIR positively correlated with both levels of 1,25(OH)(2)D and BMD, and 1,25-25-R positively and significantly correlated with levels of BMD. In T2DM or IR, IRH is a precipitating factor for bone loss. IR seems to play a major role in the pathogenesis of both IRH and bone loss in T2DM.

Renal injury, abnormal vitamin D metabolism and bone homeostasis in aged rats with insulin resistance or type 2 diabetes mellitus.

OBJECTIVE: The study aimed to explore the relationship among renal injury, abnormal vitamin D metabolism, and bone homeostasis in insulin resistance (IR) or type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: The animal models of IR, T2DM, and T2DM treated with 1-alpha hydroxyvitamin D (1-alphaOHD) were established on 18-month-old male Wistar rats. Glucose infusion rates (GIR) and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D), serum 1,25-dihydroxyvitamin D (1,25-OH2D), and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured. RESULTS: Urinary albumin level in the rats with T2DM significantly increased, and there existed a significant and negative correlation between GIR and UA level in the rats with T2DM or IR. The levels of serum 25-OHD in all models were similar. The levels of serum 1,25-OH2D and BMD in the rats with IR were significantly higher than those in the rats with T2DM and were lower than those in normal control rats. In the aged rats with T2DM, administration of 1-alphaOHD had no effect on serum 25-OHD level although significantly increased the levels of serum 1,25-O2D and BMD. There existed a negative correlation between the levels of serum 1,25-(OH)2D and UA in the rats with T2DM or IR. CONCLUSIONS: In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-OH2D deficiency and is related to renal injury, and there also existed bone loss. In T2DM, both 1,25-(OH)2D deficiency and bone loss can be reversed by 1-alphaOHD.