Dyadic psycho-social interventions for stroke survivors and family caregivers: A systematic review and meta-analysis of randomized controlled trials.

AIMS AND OBJECTIVES: To describe dyadic psycho-social intervention measures and to evaluate their influence on stroke survivors and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and coping ability. BACKGROUND: Because of the importance of dyadic intervention and the seriousness of the psycho-social problems of stroke survivors and caregivers, understanding the influence of dyadic psycho-social interventions is vital. DESIGN: A systematic review and meta-analysis based on PRISMA guidelines. DATA SOURCES: Nine databases were systematically searched for randomized controlled trials submitted from 1910 to 4 July 2022. METHODS: The included papers were evaluated for quality, and quantitative data were standardly extracted and analysed by meta-analysis, followed by synthesis. The meta-analysis was carried out using Review Manager 5.4 software. RESULTS: Fifteen randomized controlled trials were included (n = 2190 for patients, and n = 1933 for caregivers). Study results showed that dyadic psycho-social interventions significantly alleviated the depressive symptoms of patients, obviously improved the ability to function independently of patients and more quickly alleviated the care burden of caregivers. CONCLUSIONS: This study provided moderate support for the benefits of dyadic psycho-social intervention in improving survivor and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and care burden. Nevertheless, due to limitations of the study, it was deemed necessary that this topic is studied further. RELEVANCE TO CLINICAL PRACTICE: This review suggests that dyadic psycho-social interventions should be considered as effective strategies for decreasing psycho-social problems of stroke survivors and caregivers, and provides evidence for the formulation of targeted intervention programs. The personalized implementation of such interventions should be the focus of clinical practice. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution.

Protective effects of alpinetin on lipopolysaccharide/d-Galactosamine-induced liver injury through inhibiting inflammatory and oxidative responses.

Alpinetin, a type of novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to have anti-inflammatory effects. The aim of this investigation was designed to reveal the protective effects of alpinetin on Lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced liver injury in mice. Alpinetin (12.5, 25, 50 mg/kg) were given 1 h before LPS and D-Gal treatment. 12 h after LPS and D-Gal treatment, the liver tissues and serum were collected. Our results showed that alpinetin treatment improved liver histology, indicating a marked decrease of inflammatory cell infiltration and restore hepatic lobular architecture. Alpinetin also inhibited liver myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Furthermore, LPS/D-Gal-induced tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) production were dose-dependently inhibited by alpinetin. Alpinetin also attenuated LPS/D-Gal-induced expression of phospho-NF-κB p65 and phospho-IκBα. In addition, alpinetin was found to increase the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In conclusion, these findings suggested that alpinetin inhibited liver injury through inhibiting NF-κB and activating the Nrf2 signaling pathway.

Quantitative volumetric imaging of normal, neoplastic and hyperplastic mouse prostate using ultrasound.

BACKGROUND: Genetically engineered mouse models are essential to the investigation of the molecular mechanisms underlying human prostate pathology and the effects of therapy on the diseased prostate. Serial in vivo volumetric imaging expands the scope and accuracy of experimental investigations of models of normal prostate physiology, benign prostatic hyperplasia and prostate cancer, which are otherwise limited by the anatomy of the mouse prostate. Moreover, accurate imaging of hyperplastic and tumorigenic prostates is now recognized as essential to rigorous pre-clinical trials of new therapies. Bioluminescent imaging has been widely used to determine prostate tumor size, but is semi-quantitative at best. Magnetic resonance imaging can determine prostate volume very accurately, but is expensive and has low throughput. We therefore sought to develop and implement a high throughput, low cost, and accurate serial imaging protocol for the mouse prostate. METHODS: We developed a high frequency ultrasound imaging technique employing 3D reconstruction that allows rapid and precise assessment of mouse prostate volume. Wild-type mouse prostates were examined (n = 4) for reproducible baseline imaging, and treatment effects on volume were compared, and blinded data analyzed for intra- and inter-operator assessments of reproducibility by correlation and for Bland-Altman analysis. Examples of benign prostatic hyperplasia mouse model prostate (n = 2) and mouse prostate implantation of orthotopic human prostate cancer tumor and its growth (n = ) are also demonstrated. RESULTS: Serial measurement volume of the mouse prostate revealed that high frequency ultrasound was very precise. Following endocrine manipulation, regression and regrowth of the prostate could be monitored with very low intra- and interobserver variability. This technique was also valuable to monitor the development of prostate growth in a model of benign prostatic hyperplasia. Additionally, we demonstrate accurate ultrasound image-guided implantation of orthotopic tumor xenografts and monitoring of subsequent tumor growth from ~10 to ~750 mm(3) volume. DISCUSSION: High frequency ultrasound imaging allows precise determination of normal, neoplastic and hyperplastic mouse prostate. Low cost and small image size allows incorporation of this imaging modality inside clean animal facilities, and thereby imaging of immunocompromised models. 3D reconstruction for volume determination is easily mastered, and both small and large relative changes in volume are accurately visualized. Ultrasound imaging does not rely on penetration of exogenous imaging agents, and so may therefore better measure poorly vascularized or necrotic diseased tissue, relative to bioluminescent imaging (IVIS). CONCLUSIONS: Our method is precise and reproducible with very low inter- and intra-observer variability. Because it is non-invasive, mouse models of prostatic disease states can be imaged serially, reducing inter-animal variability, and enhancing the power to detect small volume changes following therapeutic intervention.

Androgen deprivation triggers a cytokine signaling switch to induce immune suppression and prostate cancer recurrence.

Androgen deprivation therapy (ADT) is an effective but not curative treatment for advanced and recurrent prostate cancer (PC). We investigated the mechanisms controlling the response to androgen-deprivation by surgical castration in genetically-engineered mouse models (GEMM) of PC, using high frequency ultrasound imaging to rigorously measure tumor volume. Castration initially causes almost all tumors to shrink in volume, but many tumors subsequently recur within 5-10 weeks. Blockade of tumor necrosis factor (TNF) signaling a few days in advance of castration surgery, using a TNFR2 ligand trap, prevents regression in a PTEN-deficient GEMM. Following tumor regression, a basal stem cell-like population within the tumor increases along with TNF protein levels. Tumor cell lines in culture recapitulate these in vivo observations, suggesting that basal stem cells are the source of TNF. When TNF signaling blockade is administered immediately prior to castration, tumors regress but recurrence is prevented, implying that a late wave of TNF secretion within the tumor, which coincides with the expression of NFkB regulated genes, drives recurrence. The inhibition of signaling downstream of one NFkB-regulated protein, chemokine C-C motif ligand 2 (CCL2), prevents post-castration tumor recurrence, phenocopying post-castration (late) TNF signaling blockade. CCL2 was originally identified as a macrophage chemoattractant and indeed at late times after castration gene sets related to chemotaxis and migration are up-regulated. Importantly, enhanced CCL2 signaling during the tumor recurrence phase coincides with an increase in pro-tumorigenic macrophages and a decrease in CD8 T cells, suggesting that recurrence is driven at least in part by tumor immunosuppression. In summary, we demonstrate that a therapy-induced switch in TNF signaling, a consequence of the increased stem cell-like character of the residual tumor cells surviving ADT, induces an immunosuppressive tumor microenvironment and concomitant tumor recurrence.

TNF Signaling Is Required for Castration-Induced Vascular Damage Preceding Prostate Cancer Regression.

The mainstay treatment for locally advanced, recurrent, or metastatic prostate cancer (PrCa) is androgen deprivation therapy (ADT). ADT causes prostate cancers to shrink in volume, or regress, by inducing epithelial tumor cell apoptosis. In normal, non-neoplastic murine prostate, androgen deprivation via castration induces prostate gland regression that is dependent on TNF signaling. In addition to this direct mechanism of action, castration has also been implicated in an indirect mechanism of prostate epithelial cell death, which has been described as vascular regression. The initiating event is endothelial cell apoptosis and/or increased vascular permeability. This subsequently leads to reduced blood flow and perfusion, and then hypoxia, which may enhance epithelial cell apoptosis. Castration-induced vascular regression has been observed in both normal and neoplastic prostates. We used photoacoustic, power Doppler, and contrast-enhanced ultrasound imaging, and CD31 immunohistochemical staining of the microvasculature to assess vascular integrity in the period immediately following castration, enabling us to test the role of TNF signaling in vascular regression. In two mouse models of androgen-responsive prostate cancer, TNF signaling blockade using a soluble TNFR2 ligand trap reversed the functional aspects of vascular regression as well as structural changes in the microvasculature, including reduced vessel wall thickness, cross-sectional area, and vessel perimeter length. These results demonstrate that TNF signaling is required for vascular regression, most likely by inducing endothelial cell apoptosis and increasing vessel permeability. Since TNF is also the critical death receptor ligand for prostate epithelial cells, we propose that TNF is a multi-purpose, comprehensive signal within the prostate cancer microenvironment that mediates prostate cancer regression following androgen deprivation.

Irradiation stent insertion for inoperable malignant biliary obstruction: a meta-analysis of randomized controlled trials.

The purpose of the study was to compare the relative clinical efficacies of irradiation stent (IRS) and conventional stent (CVS) insertions for the treatment of patients with malignant biliary obstruction (MBO). Pubmed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials (RCTs) from the date of inception through to August 2020. Data analysis was performed using RevMan v5.3. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between two groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between 2 groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. Our meta-analysis demonstrates that IRS insertion can prolong stent patency and the survival of patients with MBO compared to CVS insertion.

Prostate tumor-derived GDF11 accelerates androgen deprivation therapy-induced sarcopenia.

Most prostate cancers depend on androgens for growth, and therefore, the mainstay treatment for advanced, recurrent, or metastatic prostate cancer is androgen deprivation therapy (ADT). A prominent side effect in patients receiving ADT is an obese frailty syndrome that includes fat gain and sarcopenia, defined as the loss of muscle function accompanied by reduced muscle mass or quality. Mice bearing Pten-deficient prostate cancers were examined to gain mechanistic insight into ADT-induced sarcopenic obesity. Castration induced fat gain as well as skeletal muscle mass and strength loss. Catabolic TGF-ß family myokine protein levels were increased immediately prior to strength loss, and pan-myokine blockade using a soluble receptor (ActRIIB-Fc) completely reversed the castration-induced sarcopenia. The onset of castration-induced strength and muscle mass loss, as well as the increase in catabolic TGF-ß family myokine protein levels, were coordinately accelerated in tumor-bearing mice relative to tumor-free mice. Notably, growth differentiation factor 11 (GDF11) increased in muscle after castration only in tumor-bearing mice, but not in tumor­free mice. An early surge of GDF11 in prostate tumor tissue and in the circulation suggests that endocrine GDF11 signaling from tumor to muscle is a major driver of the accelerated ADT-induced sarcopenic phenotype. In tumor-bearing mice, GDF11 blockade largely prevented castration-induced strength loss but did not preserve muscle mass, which confirms a primary role for GDF11 in muscle function and suggests an additional role for the other catabolic myokines.

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016.

TNF signaling mediates an enzalutamide-induced metastatic phenotype of prostate cancer and microenvironment cell co-cultures.

The dramatic responses tumors display to targeted therapies are limited by acquired or pre-existing mechanisms of therapy resistance. We recently discovered that androgen receptor blockade by the anti-androgen enzalutamide paradoxically enhanced metastasis and that these pro-metastatic effects were mediated by the chemoattractant CCL2. CCL2 is regulated by TNF, which is negatively regulated by androgen signaling. Thus, we asked if TNF mediates the pro-metastatic effects of enzalutamide. We found that androgen withdrawal or enzalutamide induced TNF mRNA and protein secretion in castration resistant prostate cancer (C4-2) cells, but not in macrophage-like (THP1) or myofibroblast-like (WPMY1) cells. Androgen deprivation therapy (ADT) induced autocrine CCL2 expression in C4-2 (as well as a murine CRPC cell line), while exogenous TNF induced CCL2 in THP1 and WPMY1. TNF was most potent in myofibroblast cultures, suggesting ADT induces CCL2 via paracrine interactions within the tumor microenvironment. A soluble TNF receptor (etanercept) blocked enzalutamide-induced CCL2 protein secretion and mRNA, implying dependence on secreted TNF. A small molecule inhibitor of CCR2 (the CCL2 receptor) significantly reduced TNF induced migration, while etanercept inhibited enzalutamide-induced migration and invasion of C4-2. Analysis of human prostate cancers suggests that a TNF-CCL2 paracrine loop is induced in response to ADT and might account for some forms of prostate cancer therapy resistance.

Loss of PLZF expression in prostate cancer by immunohistochemistry correlates with tumor aggressiveness and metastasis.

PLZF is a transcription repressor, which plays a critical role in development, spermatogenesis and oncogenesis. Down-regulation of PLZF has been found in various tumor cell lines. There has been virtually no tissue study on the expression of PLZF in prostate cancer (PCa). PCa is a heterogeneous disease, most of which are indolent and non-lethal. Currently there are no biomarkers that distinguish indolent from aggressive PCa; therefore there is an urgent need for such markers to provide clinical decision support. This study aimed to investigate the expression of PLZF by immunohistochemistry in different grade as well as metastatic PCa and to correlate the alteration of PLZF expression with PCa aggressiveness. We studied a total of 83 primary PCa from biopsies, 43 metastatic PCa and 8 paired primary and metastatic PCa from radical prostatectomies with lymph node dissection. Our results demonstrated that PLZF was strongly expressed in almost all (~100%) benign luminal cells (n=77) and low grade (Gleason pattern 3) PCa (n=70) and weak or absent (100%) in basal cells (n=70). Decreased or lost expression of PLZF was evidenced in 26% of high-grade (Gleason 4 and 5) primary PCa (n=70) and 84% metastatic PCa (n=43). The primary high grade PCa in the prostatectomies shared similar PLZF loss/decrease and histomorphology to that of paired parallel lymph node metastases. These data demonstrated that down-regulation of PLZF is an important molecular process for tumor progression and loss of PLZF expression detected by routine immunohistochemistry is a promising and valuable biomarker for PCa aggressiveness and metastasis in the personalized care of PCa.

Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis.

AIM: To examine whether poly-unsaturated fatty acid (PUFA) therapy is beneficial for improving nonalcoholic steatohepatitis (NASH). METHODS: In total, 78 patients pathologically diagnosed with NASH were enrolled and were randomly assigned into the control group and the PUFA therapy group (added 50 mL PUFA with 1:1 ratio of EHA and DHA into daily diet). At the initial analysis and after 6 mo of PUFA therapy, parameters of interest including liver enzymes, lipid profiles, markers of inflammation and oxidation, and histological changes were evaluated and compared between these two groups. RESULTS: At the initial analysis, in patients with NASH, serum levels of alanine aminotransferase (ALT) and aspartase aminotransferase (AST) were slightly elevated. Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol levels, markers of systemic inflammation [C-reactive protein (CRP)] and oxidation [malondialdehyde (MDA)], as well as fibrosis parameters of type IV collagen and pro-collagen type III pro-peptide were also increased beyond the normal range. Six months later, ALT and AST levels were significantly reduced in the PUFA group compared with the control group. In addition, serum levels of TG and TC, CRP and MDA, and type IV collagen and pro-collagen type III pro-peptide were also simultaneously and significantly reduced. Of note, histological evaluation showed that steatosis grade, necro-inflammatory grade, fibrosis stage, and ballooning score were all profoundly improved in comparison to the control group, strongly suggesting that increased PUFA consumption was a potential way to offset NASH progression. CONCLUSION: Increased PUFA consumption is a potential promising approach for NASH prevention and reversal.

Regulation of ethanol-related behavior and ethanol metabolism by the Corazonin neurons and Corazonin receptor in Drosophila melanogaster.

Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in ethanol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of ethanol metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from ethanol-induced sedation that we refer to as hangover-like phenotype. Newly generated mutant lacking Crz Receptor (CrzR(01) ) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR(01) mutant following ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR(01) mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR(01) . Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and Adh mRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR(01) mutant. These findings suggest that CrzR-associated signaling pathway is critical for ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated ethanol-related behavior and metabolism.

Luteolin decreases the attachment, invasion and cytotoxicity of UPEC in bladder epithelial cells and inhibits UPEC biofilm formation.

Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is one of the most common infectious diseases worldwide. Emerging antibiotic resistance requires novel treatment strategies. Luteolin, a dietary polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent. Here, we evaluated the sub-MICs of luteolin for potential properties to modulate the UPEC infection. We found that luteolin significantly decreased the attachment and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24. Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene, lower bacterial surface hydrophobicity and swimming motility, were observed in luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced cytotoxicity in T24 cells, which manifested as decreased activity of lactate dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally, the luteolin-pretreated UPEC showed a lower ability of biofilm formation. Collectively, these results indicated that luteolin decreased the attachment and invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced cytotoxicity and biofilm formation via down-regulating the expression of adhesin fimH gene, reducing the bacterial surface hydrophobicity and motility.

Characterization, expression, and evolutionary aspects of Corazonin neuropeptide and its receptor from the House Fly, Musca domestica (Diptera: Muscidae).

In this article, we characterized structure and expression of genes encoding the neuropeptide Corazonin (MdCrz) and its putative receptor (MdCrzR) in the House Fly, Musca domestica. The MdCrz gene contains two introns, one within the 5' untranslated region and the other within the open reading frame. The 150-amino-acid precursor consists of an N-terminal signal peptide, and mature Crz followed by Crz-associated peptide (CAP). The CAP region is highly diverged from those of other insect precursors, whereas the mature Crz is identical in other dipteran members. In situ hybridization and immunohistochemistry consistently found a group of three MdCrz-producing neurons in the dorso-lateral protocerebrum, and eight pairs of bi-lateral neurons in the ventral nerve cord in the larvae. In adults, the expression was found exclusively in a cluster of five to seven neurons per brain lobe. Comparable expression patterns observed in other dipteran species suggest conserved regulatory mechanisms of Crz expression and functions during the course of evolution. MdCrzR deduced from the full-length cDNA sequence is a 655-amino acid polypeptide that contains seven trans-membrane (TM) domains and other motifs that are characteristics of Class-A G-protein coupled receptors. Although the TMs and loops between the TMs are conserved in other CrzRs, N-terminal extracellular domain is quite dissimilar. Tissue-specific RT-PCR revealed a high level of MdCrzR expression in the larval salivary glands and a moderate level in the CNS. In adults, the receptor was expressed both in the head and body, suggesting multifunctionality of the Crz signaling system.

[Surveillance on Keshan disease from 1990 to 2008 in Sichuan province].

OBJECTIVE: To study the epidemiological characteristics of Keshan disease (KD) and its trend so as to provide evidences for further research, prevention and treatment of the disease in Sichuan province. METHODS: Based on KD related data from 1990 to 2008, descriptive method was used to analyze the epidemiological characteristics of KD. RESULTS: 87 KD cases were identified during the 19 years. All cases were children from the countryside, with majority of them were Yi nationality. Age of the patients ranged from 5 months to 18 years, with majority at 2 - 6 year-olds. The annual incidence rates were from 0/100 000 to 1.73/100 000 with 1999 the highest (1.73/100 000). A total number of 310 preclinical or chronic KD cases were identified and the total detection rates were between 0.28% and 2.8%, with 1992 the highest. As for levels of blood selenium during the 19 years: 1995 appeared the lowest (0.1345 microg/g), followed by 1990 - 2000 (0.1558 microg/g) but all of them fell in to the level in the KD epidemic areas. CONCLUSION: There were 5 stages in the development trend of KD disease in Sichuan province, with 2 ascending and 3 descending. The differences between any of the two stages were statistically significant. The 3 descending stages all appeared right after the selenium supplement intervention was taken. Our data showed that the program of selenium supplement was closely related to the incidence of KD, suggesting that a long term mechanism of Selenium supplement in the epidemic areas should be taking into account.