Low molecular weight heparin promotes the PPAR pathway by protecting the glycocalyx of cells to delay the progression of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most important comorbidities for diabetic patients, which is the main factor leading to end-stage renal disease. Heparin analogues can delay the progression of DN, but the mechanism is not fully understood. In this study, we found that low molecular weight heparin (LMWH) therapy significantly upregulated some downstream proteins of the peroxisome proliferator-activated receptor (PPAR) signaling pathway by label-free quantification of the mouse kidney proteome. Through cell model verification, LMWH can protect the heparan sulfate (HS) of renal tubular epithelial cells from being degraded by heparanase that is highly expressed in a high-glucose environment, enhance the endocytic recruitment of fatty acid-binding protein 1 (FABP1), a coactivator of the PPAR pathway, and then regulate the activation level of intracellular PPAR. In addition, we have elucidated for the first time the molecular mechanism of HS and FABP1 interaction. These findings provide new insights into understanding the role of heparin in the pathogenesis of DN and developing corresponding treatments.

Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

Identification of Potential Indicators for Survival in Patients with Thyroid Cancer Based on Expression of FAM3 Members.

Thyroid cancer (THCA) is a common head and neck malignancy. The family with sequence similarity 3 (FAM3) is a cytokine-like gene family with four members, which is presumed to participate in the development of many cancer types. However, the expression patterns of FAM3s in THCA and their prognostic values, have not yet been established. We investigated differential expressions of FAM3 mRNA and protein in THCA, then validated the findings for FAM3B by immunohistochemistry. We also investigated survival data with respect to FAM3 expression patterns in patients with THCA. FAM3s information regarding their relationships with clinical pathological parameters were obtained and FAM3 mutations were assessed. KEGG and GO pathway regarding FAM3C were obtained using online databases. To investigate potential correlations between FAM3s and immune cell infiltration, we investigated the roles of FAM3s in immune cells of patients with THCA. The mRNA expression of FAM3C were significantly elevated in THCA tissues; high expression levels of FAM3C protein were also observed in THCA tissues. A significant association between the pathological stage and the expression of FAM3C was found in patients with THCA. Patients with THCA who had high mRNA expression levels of FAM3C exhibited significantly more favorable prognosis, compared with patients who had low mRNA expression levels of FAM3C. Overall, FAM3C may play vital roles in the pathogenesis and development of THCA, and these findings constitute novel insights for biomarkers of immunotherapeutic targeted agents and may aid in the identification of prognostic biomarkers for THCA.

Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling.

Metabolic diseases pose a significant global health challenge, characterized by an imbalance in metabolism and resulting in various complications. Secreted frizzled-related protein 5 (SFRP5), an adipokine known for its anti-inflammatory properties, has gained attention as a promising therapeutic target for metabolic diseases. SFRP5 acts as a key regulator in the Wnt signaling pathway, exerting its influence on critical cellular functions including proliferation, differentiation, and migration. Its significance extends to the realm of adipose tissue biology, where it plays a central role in regulating inflammation, insulin resistance, adipogenesis, lipid metabolism, glucose homeostasis, and energy balance. By inhibiting Wnt signaling, SFRP5 facilitates adipocyte growth, promotes lipid accumulation, and contributes to a decrease in oxidative metabolism. Lifestyle interventions and pharmacological treatments have shown promise in increasing SFRP5 levels and protecting against metabolic abnormalities. SFRP5 is a pivotal player in metabolic diseases and presents itself as a promising therapeutic target. An overview of SFRP5 and its involvement in metabolic disorders and metabolism is provided in this comprehensive review. By elucidating these aspects, valuable insights can be gained to foster the development of effective strategies in combating metabolic diseases.

Human cytomegalovirus infection is associated with stroke in women: the US National Health and Nutrition Examination Survey 1999-2004.

BACKGROUND: Increasing evidence indicated that infection factors play important roles in stroke development. Human cytomegalovirus (HCMV) infection was positively associated with atherosclerosis and hypertension which are stroke risk factors. Therefore, we aimed to explore the relationship between HCMV infection and stroke using the data of US National Health and Nutrition Examination Survey (NHANES). METHODS: We analysed data on 2844 men and 3257 women in the NHANES 1999-2004. We included participants aged 20-49 years who had valid data on HCMV infection and stroke. RESULTS: 54.1% of participants had serological evidence of HCMV infection and 0.8% of them had a previous diagnosis of stroke. There were ethnic differences in the prevalence of HCMV seropositivity (p<0.001). There was no significant association between HCMV seropositivity and stroke in men in any of the models. In women, HCMV seropositivity was associated with stroke before adjustment (OR=3.45, 95% CI 1.09 to 10.95, p=0.036). After adjusting for race/ethnicity, the association remained significant (OR=4.40, 95% CI 1.37 to 14.09, p=0.014). After further adjustment for body mass index, diabetes, hypercholesterolaemia, hypertension, alcohol consumption, smoking and physical activity, the association still existed (OR=3.58, 95% CI 1.14 to 11.25, p=0.030). The association was significant consistently in adjusted model for age (OR=3.39, 95% CI 1.08 to 10.64, p=0.037). CONCLUSIONS: We found a strong association between HCMV and stroke in women from the nationally representative population-based survey. This provide additional motivation for undertaking the difficult challenge to reduce the prevalence of stroke.

Fertility intentions among the working population of Dalian City born between 1980 and 1989.

In October 2015, the Chinese Government announced that the one-child policy had finally been replaced by a universal two-child policy. China's universal two-child policy is highly significant because, for the first time in 36 years, no one in an urban city is restricted to having just one child. This cross-sectional study was conducted to explore future fertility intentions and factors influencing individual reproductive behaviour (whether to have two children) in Dalian City. A total of 1370 respondents were interviewed. The respondents' mean ideal number of children was only 1.73, and urban respondents' sex preference was symmetrical. A total of 19.0% of the respondents were unmarried, 64.5% were married and had childbearing experience and only 6.3% of married respondents had two children. Among the 1370 participants, 30.4% stated that they would have a second child, while 69.6% refused to have a second child in the future. Binary logistic regression analysis (Model 1) showed that the following characteristics were associated with having only one child in the future: being female, being older, having a lower education level, being born in Dalian, having a lower family income and reporting one child as the ideal number of children. Model 2 (comprising only respondents with childbearing experience) showed that respondents who were female, had a lower family income and were unable to obtain additional financial support from parents were more likely to intend to stick at one child. In addition, respondents' ideal number of children and childbearing experiences had a significant influence on future fertility intentions. These results suggest that fertility intentions and reproductive behaviours are still below those needed for replacement level fertility in Dalian City. China's policymakers should pay more attention to these factors (socioeconomic characteristics, economic factors, desired number of children and childbearing experiences) and try to increase individual reproductive behaviour.

Time-dependence of NIHSS in predicting functional outcome of patients with acute ischemic stroke treated with intravenous thrombolysis.

OBJECTIVES: The National Institute of Health Stroke Scale (NIHSS) is a predictor for the prognosis of acute ischaemic stroke (AIS) and its prediction is time-dependent. We examined the performance of NIHSS at different timepoints in predicting functional outcome of patients with thrombolysed AIS. METHODS: This prospective study included 269 patients with AIS treated with recombinant tissue plasminogen activator (rt-PA). Unfavourable functional outcome was defined as modified Rankin Scale score 4-6 at 3 months after rt-PA treatment. Receiver operating characteristic curves were used to examine the predictive power of NIHSS score at admission and 2 hours/24 hours/7 days/10 days after rt-PA treatment. Youden's index was used to select the threshold of NIHSS score. Logistic regression was used to estimate the ORs of unfavourable functional outcome for patients with NIHSS score higher than the selected thresholds. RESULTS: The threshold of NIHSS score at admission was 12 (sensitivity: 0.51, specificity: 0.84) with an acceptable predictive power (area under curve [AUC] 0.74) for unfavourable functional outcome. The threshold changed to 5 at 24 hours after rt-PA treatment (sensitivity: 0.83, specificity: 0.65) and remained unchanged afterwards. The predictive power and sensitivity sequentially increased over time and peaked at 10 days after rt-PA treatment (AUC 0.92, sensitivity: 0.85, specificity: 0.80). NIHSS scores higher than the thresholds were associated with elevated risk of unfavourable functional outcome at all timepoints (all p<0.001). CONCLUSIONS: NIHSS is time-dependent in predicting AIS prognosis with increasing predictive power over time. Since patients whose NIHSS score ≥ 12 are likely to have unfavourable functional outcome with rt-PA treatment only, mechanical thrombectomy should be largely taken into consideration for these patients.

Application of a modified thoracoabdominal approach that avoids cutting open the costal portion of diaphragm during anterior thoracolumbar spine surgery.

PURPOSE: In the present prospective randomized controlled study, we compared the feasibility and effectiveness of our modified thoracoabdominal approach to anterior thoracolumbar spine surgery without cutting open the costal portion of diaphragm (extradiaphragmatic approach) with the traditional transdiaphragmatic thoracoabdominal approach. The traditional combined thoracoabdominal approach in anterior thoracolumbar surgery for spine tuberculosis is effective but seriously damages the diaphragm and causes various lung complications. We used an extradiaphragmatic approach for complete anterior debridement, bone grafting, and nerve decompression and compared its efficacy and complications with those of the traditional transdiaphragmatic thoracolumbar approach. METHODS: The study included 106 patients with spinal tuberculosis. After a standard preoperative chemotherapy regimen, all patients underwent posterior deformity correction and internal fixation, anterior debridement, decompression, and bone grafting. Patients were divided into the modified extradiaphragmatic thoracolumbar approach group (the modified group) and the traditional transdiaphragmatic thoracolumbar approach group (the traditional group). During the treatment, we strictly followed the standard chemotherapy regimen. RESULTS: The mean follow-up duration was 36.2 months (range 25-38 months). There were significant differences between the two groups in intraoperative blood loss, length of incision, recovery time, and postoperative complications but no significant differences in preoperative and postoperative erythrocyte sedimentation rates and C-reactive protein values, kyphosis, and neurologic function, recovery of ability to live and work, and postoperative healing of bone grafts. CONCLUSION: The modified extradiaphragmatic thoracolumbar approach for anterior thoracolumbar spine surgery is as effective as the traditional approach. However, associated surgical trauma is minimal, and the incidence of pulmonary complications is low.

Lycium barbarum L. Polysaccharide (LBP) Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell.

Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.

A study of the association between atmospheric particulate matter and blood pressure in the population.

This systematic review and meta-analysis was conducted to assess the association between the level of atmospheric particulate matter (PM) and the increase in blood pressure (BP) for different exposure terms (≤ 7 vs > 7 days) and age groups (< 65 vs ≥ 65 years). Some databases were searched to investigate the association between increased atmospheric PM (diameter < 2.5 mm [PM2.5] or < 10 mm [PM10]) and BP (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). Among a total of 719 identified articles, 68 were reviewed in depth, of which only 20 satisfied the inclusion criteria. A significant association was found between PM10 levels and higher BP. The ß values were 0.270mmHg (95% confidence interval [CI] 0.068-0.482) for SBP and 0.215mmHg (95% CI 0.058-0.372) for DBP. These ß values mean that, for every 10 mg/m(3) increase in PM10, SBP increased by 0.270mmHg and DBP by 0.215 mmHg. Subgroup analyses were conducted for different exposure terms and age groups. A positive association was seen between PM2.5 and SBP. The ß value of SBP was 0.495mmHg (95% CI 0.03-0.96) with every 10 mg/m(3) increase in PM2.5. There were no significant associations in both age groups and non-older groups. There was no significant association between PM2.5 and DBP, either in the overall effect or in the subgroup effects. In conclusion, significant associations were found between higher BP and higher PM10 levels, but the association between BP and levels of PM2.5 levels was unclear.

The China Mental Health Survey: II. Design and field procedures.

China Mental Health Survey (CMHS), which was carried out from July 2013 to March 2015, was the first national representative community survey of mental disorders and mental health services in China using computer-assisted personal interview (CAPI). Face-to-face interviews were finished in the homes of respondents who were selected from a nationally representative multi-stage disproportionate stratified sampling procedure. Sample selection was integrated with the National Chronic Disease and Risk Factor Surveillance Survey administered by the National Centre for Chronic and Non-communicable Disease Control and Prevention in 2013, which made it possible to obtain both physical and mental health information of Chinese community population. One-stage design of data collection was used in the CMHS to obtain the information of mental disorders, including mood disorders, anxiety disorders, and substance use disorders, while two-stage design was applied for schizophrenia and other psychotic disorders, and dementia. A total of 28,140 respondents finished the survey with 72.9% of the overall response rate. This paper describes the survey mode, fieldwork organization, procedures, and the sample design and weighting of the CMHS. Detailed information is presented on the establishment of a new payment scheme for interviewers, results of the quality control in both stages, and evaluations to the weighting.

Chronic hypoxia facilitates Alzheimer's disease through demethylation of γ-secretase by downregulating DNA methyltransferase 3b.

INTRODUCTION: Environmental factors and epigenetic mechanisms are believed to contribute to Alzheimer's disease (AD). We previously documented that prenatal hypoxia aggravated the cognitive impairment and neuropathology in offspring mice. Here, we investigate the chronic hypoxia-induced epigenetic modifications in AD. METHODS: The 3-month-old APP(swe)/PS1(dE9) mice were exposed to hypoxic environment 6 hour/day for 30 days, followed by learning and memory tests and biochemical and neuropathology measurement at the age of 4, 6, and 9 months. RESULTS: We found hypoxia exaggerated the neuropathology and cognitive impairment in AD mice. Chronic hypoxia induced demethylation on genomic DNA and decreased the expression of DNA methyltransferase 3b (DNMT3b) in vivo. We further found that DNMTs inhibition elevated the protein levels of amyloid precursor protein, ß- and γ-secretases, whereas overexpression of DNMT3b suppressed the levels of them in vitro. DISCUSSION: Our study suggests chronic hypoxia can aggravate AD progression through demethylation of genes encoding γ-secretase components by downregulation of DNMT3b.

Association of depression with inflammation in hospitalized patients of myocardial infarction.

OBJECTIVE: The aim of this study was to examine the associations between depression and inflammatory markers in patients admitted to the hospital for myocardial infarction. METHODS: Inflammatory cytokines, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were assessed in a group of 75 depressed participants (score of ≥ 12) and compared to a control group of 75 nondepressed participants (score < 12), all who had been admitted to the hospital for myocardial infarction. The presence of depressive symptoms was assessed using the Beck Depressive Symptoms Inventory II Scale (BDI-II). RESULTS: Depressed myocardial infarction participants had significantly greater levels of TNF-α (t = 2.070, P < 0.05) compared with control myocardial infarction participants. The BDI-II score was positively correlated with TNF-α levels (r = 0.222, P < 0.05). CONCLUSIONS: These results indicate that the presence of depressive symptoms is positively associated with TNF-α levels among patients who have suffered from myocardial infarction.

[Prudent use price controls in Chinese medicines market: based on statistical data analysis].

A dispute about the decreasing-price problem of traditional Chinese medicine (TCM) has recently arisen. This article analyzes the statistical data of 1995-2011 in China, the results showed that the main responsibility of expensive health care has no direct relationship with the drug price. The price index of TCM rose significantly slower than the medicine prices, the production margins of TCM affected by the material prices has been diminishing since 1995, continuous price reduction will further depress profits of the TCM industry. Considering the pros and cons of raw materials vary greatly in price, decreasing medicine price behavior will force enterprises to use inferior materials in order to maintain corporate profits. The results have the guiding meaning to medicine price management.

Emerging therapeutic landscape: Incretin agonists in chronic kidney disease management.

The increasing incidence of chronic kidney disease (CKD) poses a significant public health concern, prompting heightened attention to its treatment. Incretins, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide, are intestinal peptides released after nutrient intake, known for their hypoglycemic effects in diabetes management. Recent advancements highlight the promising outcomes of GLP-1 receptor agonists in reducing CKD risk factors and improving renal outcomes. The multifaceted functions of GLP-1, such as its anti-obesity, anti-hypertensive, anti-hyperglycemic, anti-lipid, anti-inflammatory, and endothelial function protective properties, contribute to its potential as a therapeutic agent for CKD. Although experiments suggest the potential benefits of incretin in CKD, a comprehensive understanding of its specific mechanisms is still lacking. This review aims to provide a detailed examination of current evidence and potential future directions, emphasizing the promising yet evolving landscape of incretin agonists in the context of CKD.

Environmental toxicology of bisphenol A: Mechanistic insights and clinical implications on the neuroendocrine system.

Bisphenol A (BPA) is a widely used environmental estrogen found in a variety of products, including food packaging, canned goods, baby bottle soothers, reusable cups, medical devices, tableware, dental sealants, and other consumer goods. This substance has been found to have detrimental effects on both the environment and human health, particularly on the reproductive, immune, embryonic development, nervous, endocrine, and respiratory systems. This paper aims to provide a comprehensive review of the effects of BPA on the neuroendocrine system, with a primary focus on its impact on the brain, neurons, oligodendrocytes, neural stem cell proliferation, DNA damage, and behavioral development. Additionally, the review explores the clinical implications of BPA, specifically examining its role in the onset and progression of various diseases associated with the neuroendocrine metabolic system. By delving into the mechanistic analysis and clinical implications, this review aims to serve as a valuable resource for studying the impacts of BPA exposure on organisms.

The impact of the senescent microenvironment on tumorigenesis: Insights for cancer therapy.

The growing global burden of cancer, especially among people aged 60 years and over, has become a key public health issue. This trend suggests the need for a deeper understanding of the various cancer types in order to develop universally effective treatments. A prospective area of research involves elucidating the interplay between the senescent microenvironment and tumor genesis. Currently, most oncology research focuses on adulthood and tends to ignore the potential role of senescent individuals on tumor progression. Senescent cells produce a senescence-associated secretory phenotype (SASP) that has a dual role in the tumor microenvironment (TME). While SASP components can remodel the TME and thus hinder tumor cell proliferation, they can also promote tumorigenesis and progression via pro-inflammatory and pro-proliferative mechanisms. To address this gap, our review seeks to investigate the influence of senescent microenvironment changes on tumor development and their potential implications for cancer therapies.

Ultra-short-course chemotherapy for spinal tuberculosis: five years of observation.

PURPOSE: This study aimed to explore the feasibility of ultra-short-course chemotherapy in the treatment of spinal tuberculosis. METHODS: One hundred and eighty-five patients with confirmed spinal tuberculosis and surgical indication were included. The chemotherapy regimen was 2SHRZ/XHRZ. According to the duration of the chemotherapy, the patients were divided into two groups, the ultra-short-course chemotherapy group with an average duration of 4.5 months, and the standard chemotherapy group with an average duration of 9 months. The same surgery was performed for patients in the two groups. RESULTS: The duration of the follow-up ranged from 61 to 87 months, with an average of 69.1 months. Erythrocyte sedimentation rate and C-reactive protein, kyphosis and nerve function, recovery of work, and activities of daily living were not significantly different between the two groups before or after treatment; however, the aforementioned indices were significantly different before and after treatment within groups. There was no significant difference in postoperative bone graft healing between the two groups. The drug side effects were significantly different between the two groups. CONCLUSIONS: With thorough focus debridement, bone grafting, and internal fixation, the efficacy of ultra-short chemotherapy was similar to that of standard chemotherapy for the treatment of spinal tuberculosis. The ultra-short-course chemotherapy can shorten the course of treatment and reduce drug side effects.

[Optimal culture conditions of transgenic Polygonium multiflorum hairy root and the effect of elicitor on its growth].

OBJECTIVE: To optimize the culture medium of transgenic Polygonium multiflorum hairy root and the effect of different elicitors on its growth. METHODS: Measured the growth curve of hairy root in four media, including MS, 1/2 MS, B5 and White and estimated the effects of elicitors on the hairy root biomass. RESULTS: MS medium was the most suitable of the four media for hairy root growth. The different concentrations of elicitors, salicylic acid and methyl jasmonate, inhibited the biomass accumulation of hairy root. CONCLUSION: MS is the optimum medium for transgenic Polygonium multiflorum hairy root. Two usual plant elicitors, salicylic acid and methyl jasmonate, can inhibit the growth of transgenic hairy root.

The protective effects of SGLT-2 inhibitors, GLP-1 receptor agonists, and RAAS blockers against renal injury in patients with type 2 diabetes.

Diabetic kidney disease is one of the most severe complications of type 2 diabetes mellitus. Patients with diabetic kidney disease have a worse prognosis in terms of mortality and morbidity, compared with patients who have diabetes alone. Strict control of blood pressure and blood glucose is the primary method for prevention of initial kidney damage and delaying further progression of existing damage. Other management approaches include the use of exogenous drugs that can effectively protect the kidneys from diabetes, such as sodium-glucose transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and renin-angiotensin-aldosterone system blockers. These drugs may protect against kidney injury through various molecular mechanisms. This review focuses on renal impairment in patients with type 2 diabetes; it discusses the direct and indirect effects of sodium-glucose transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and renin-angiotensin-aldosterone system blockers on diabetic kidney disease. Finally, it discusses the effects of combination treatment with two or three types of drugs in patients with chronic kidney disease.