Modifiable Lifestyle, Sedentary Behaviors and the Risk of Frailty: A Univariate and Multivariate Mendelian Randomization Study.

This research conducted a two-sample univariate and multivariate Mendelian Randomization (MR) analysis to explore the causal link between different types of leisure sedentary behavior (LSB) and frailty. Independent instrumental variables significantly associated with sedentary behaviors (p < 5 × 10-8) are obtained from a genome-wide association study (GWAS) of 422,218 individuals, and Frailty Index (FI) are derived from the latest GWAS dataset of 175,226 individuals. MR analysis is conducted using inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode, supplemented by MRAPSS. Univariate MR revealed that sedentary behaviors such as watching television increased the risk of frailty (OR, 1.271; 95% CI: 1.202-1.345; p = 6.952 × 10-17), as sedentary driving behaviors are done (OR, 1.436; 95% CI: 1.026-2.011; p = 0.035). Further validation through APSS, taking into account cryptic relatedness, stratification, and sample overlap, maintained the association between television viewing and increased frailty risk (OR, 1.394; 95% CI: 1.266-1.534; p = 1.143 × 10-11), while the association with driving dissipated. In multivariate inverse variance weighted (IVW) analysis, after adjusting for C-reactive protein (CRP) levels, television Sedentary behavior (SB) inversely affected frailty (OR, 0.782; 95% CI: 0.724-0.845; p = 4.820 × 10-10). This study indicates that televisio SB significantly increases the risk of frailty, suggesting potential biological heterogeneity behind specific sedentary activities. This process may interact with inflammation, influencing the development of frailty.

Eczema as a protective factor for brain cancer: a meta-analysis.

BACKGROUND: Brain cancer is one of the most aggressive cancer types owing to poor treatment effects. Epidemiological studies have demonstrated that allergies may increase the disease risk. Therefore, this study evaluated the association between eczema and the risk of various brain cancers. METHODS: We systematically searched the PubMed and Embase databases from their inception until June 23, 2022. Two reviewers independently reviewed and screened the articles, extracted data, assessed the study quality, and pooled the results. Stata software was used to generate pooled odds ratios and 95% confidence intervals (CIs). RESULTS: We included 20 studies comprising 5,117,222 patients that investigated the relationship between eczema and brain cancer. Eczema was significantly inversely associated with the risk of brain cancer (odds ratio [OR], 0.82; 95% CI, 0.77-0.87), glioma (OR, 0.53; 95% CI, 0.14-2.02), meningioma (OR, 0.74; 95% CI, 0.66-0.84), and acoustic neuroma (OR, 0.60; 95% CI, 0.41-0.88). Interesting, The strong correlation between eczema and the reduced risk of brain cancer was observed in people over 16 years old (OR, 0.79; 95% CI, 0.71-0.88), but not in those under 16 years old (OR, 0.94; 95% CI, 0.79-1.11). In addition, subgroup analyses found that eczema significantly decreased the glioma risk in Europeans (OR, 0.73; 95% CI, 0.65-0.82) but not Australians (OR, 0.53; 95% CI, 0.14-2.02) or Americans (OR, 1.01; 95% CI, 0.69-1.46). CONCLUSION: Eczema may be considered as a potential protective factor of brain cancer in population aged over 16 years. However, this relationship requires verification using large-scale clinical data.

Potential Correlation Between Eczema and Hematological Malignancies Risk: A Systematic Review and Meta-Analysis.

Background: Eczema characterized by itch, sleeplessness, and adverse effects on quality of life is associated with a risk of hematological malignancies. However, there is a controversy pertaining to whether this association implies a greater or lesser risk of hematological cancers. We aimed to explore the link between eczema and hematological malignancies risk. Methods: We systematically searched PubMed and Embase databases from their inception to February 17, 2022. Two reviewers independently screened articles, extracted data and assessed study quality, respectively. The odds ratios and 95% confidence intervals (CIs) were pooled by using fixed or random-effects models. Results: 29 studies involving 2,521,574 participants examined the contribution of eczema to hematological malignancies. We found that eczema significantly increased the risk of Hodgkin's lymphoma (1.44; 95% CI, 1.07-1.95), myeloma (1.15; 95% CI, 1.04-1.28), and significantly decreased the risk of lymphocytic leukemia (0.91; 95% CI, 0.84-0.99); however, it is not significantly associated with Non-Hodgkin's lymphoma, and myelocytic leukemia. Conclusion: Eczema has been shown to be associated with the risk of hematological cancer, this association still needs to be verified in large randomized controlled trials. Systematic Review Registration: https://inplasy.com/, INPLASY202260097.

Does the green credit policy affect the scale of corporate debt financing? Evidence from listed companies in heavy pollution industries in China.

The current study constructs a quasi-natural experiment based on China's 2012 Green Credit Guidelines and develops a difference-in-difference model using the financial data of listed companies from 2006 to 2018 to conduct empirical testing. The results reveal that the green credit policy has significantly reduced the short-term and long-term debt financing of heavily polluting enterprises; however, the restrictions on short-term debt financing are insufficient. At the same time, the decline in operating performance brings financial penalty effects, among which state-owned, large-scale, and heavily polluting enterprises in high-emission areas have strong financial penalty effects. The green credit policy encourages heavy-polluting companies to increase R&D investment and increase fixed assets investments to obtain long-term credit support with short-term investment. Furthermore, it is found that the green credit policies have significantly restrained the scale of debt financing of heavily polluting companies. The Chinese government should formulate green financial policies based on local conditions and provide credit resources to favor environmentally friendly companies. Financial institutions should strictly implement green credit standards and modify financial products and services. Companies should take the initiative to eliminate outdated production capacity to obtain green credit support.

Identification of an unrecognized circRNA associated with development of renal fibrosis.

Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive. Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly. Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis. Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.

Aberrant DNA methylation of Cyclind-CDK4-p21 is associated with chronic fluoride poisoning.

Endemic fluorosis is a serious problem in public health, affecting thousands of people. Abnormal proliferation and activation of osteoblasts in skeletal fluorosis lesions play a leading role and osteoblast proliferation is finely regulated by the cell cycle. There are a few reports on fluoride-induced DNA methylation. However, the role of DNA methylation of the cyclin/cyclin-dependent kinase (CDK)/cyclin-dependent kinase inhibitor (CKI) regulatory network in skeletal fluorosis has not been investigated. We used a population study and in vitro experiment to explore the relationship between the pathogenesis of skeletal fluorosis and methylation of Cyclin d1/CDK4/p21. The results showed a positive relationship between fluoride exposure and expression of Cyclin d1/CDK4, and a negative relationship between fluoride exposure and expression of P21. Hypermethylation of p21 was found in the fluoride-exposed population, and low expression of p21 attributed to promoter hypermethylation was confirmed in vitro. However, no changes in methylation levels of Cyclin d1 and CDK4 genes were observed in the population exposed to fluoride and NaF-treated osteoblasts. These results show that methylation of p21 gene has a significant impact on the proliferation of osteoblasts during the development of skeletal fluorosis. The present study was a first attempt to link the methylation of the Cyclin d1/CDK4/p21 regulatory network with osteoblast proliferation in skeletal fluorosis.

Aberrant methylation-induced dysfunction of p16 is associated with osteoblast activation caused by fluoride.

Chronic exposure to fluoride continues to be a public health problem worldwide, affecting thousands of people. Fluoride can cause abnormal proliferation and activation of osteoblast and osteoclast, leading to skeletal fluorosis that can cause pain and harm to joints and bones and even lead to permanent disability. Nevertheless, there is no recognized mechanism to explain the bone lesions of fluorosis. In this work, we performed a population study and in vitro experiments to investigate the pathogenic mechanism of skeletal fluorosis in relation to methylation of the promoter of p16. The protein coded by the p16 gene inhibits cdk (cyclin-dependent kinase) 4/cdk6-mediated phosphorylation4 of retinoblastoma gene product and induces cell cycle arrest. The results showed that hypermethylation of p16 and reduced gene expression was evident in peripheral blood mononuclear cells of patients with fluorosis and correlated with the level of fluoride exposure. Studies with cell cultures of osteoblasts revealed in response to sodium fluoride (NaF) treatment, there was an induction of p16 hypermethylation and decreased expression, leading to increased cell proliferation, a longer S-phase of the cell cycle, and development of skeletal fluorosis. Further, the methylation inhibitor, 5-aza-2-deoxycytidine, reversed the p16 hypermethylation and expression in response to NaF. These results reveal a regulatory role of p16 gene methylation on osteoblasts activation during the development of skeletal fluorosis.

[Increased expression of KCTD9, a novel potassium channel related gene, correlates with disease severity in patients with viral hepatitis B].

OBJECTIVE: Studies have shown that potassium channel plays a pivotal role in T cell activation. The expression of potassium channel gene KCTD9 was evidenced being highly upregulated in patients with severe hepatitis B (SHB). To understand this phenomenon further, tissue and cellular expression profiles of KCTD9 were investigated in patients with SHB. METHODS: A rabbit peptide polyclonal antibody was prepared. Various samples including peripheral blood mononuclear cells (PBMCs); livers from patients with SHB or mild chronic hepatitis B, were examined for KCTD9 expression by quantitative real time PCR and immunohistochemistry staining (IHC). Confocal microscopy was used to illustrate the localizations of the expressions. RESULTS: Increased expression of KCTD9 was observed in PBMC in over 35.7% of the patients with SHB when compared with that of patients with mild chronic hepatitis B. In all patients, the relative value of increased KCTD9 mRNA was positively correlated with alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin but negatively with serum albumin. The expression was mainly located in hepatocytes, bile duct epithelial cells, Kupffer cells and inflammatory cells, and in the cytoplasm of PBMCs from the healthy individuals and patients with mild chronic hepatitis B, whereas in both cytoplasm and nuclei in those from patients with SHB. CONCLUSION: The increased expression of potassium channel gene KCTD9 correlates with disease severity in patients with viral hepatitis B.

[Effects of serum containing oral liquid of Guilu-Erxian on the therapy of osteoporosis at the cellular level].

This study sought to assess the effects of serum containing Guilu-Erxian (GLEX) on treating osteoporosis at the cellular level. First, Enzyme-digestion was used to obtain osteoblasts from newborn SD rats. Alkaline phosphatase staining was used to identify osteoblasts. The proliferation and the secretion of Insulin Like Growth Factor-1 (IGF-1) of osteoblasts were examined. Second, osteoclasts were generated by inducing bone marrow cells of SD male rat (6-9 weeks) with 1,25(OH)2D3. The osteoclasts were identified through tartrate-resistant acid phosphatase (TRAP) staining. Bone pits of osteoclasts were observed through Electron Scanning Microscope. At the same time, TRAP(+) cells with more than two nuclei and TRAP activity of osteoclasts were examined. Last, serum containing Guilu-Erxian was made through serum pharmacology. And we observed the effects of serum containing Guilu-Erxian on the function of osteoblasts and osteoclasts. We found that high doses of serum containing Guilu-Erxian had obvious effects on stimulating the multiplication and capability of secreting IGF-1 of osteoblasts cultured in vitro. Middle doses obviously inhibited the formation of osteoclasts and bone pits; TRAP activity of osteoclasts was also lowered clearly. This study indicated that Guilu-Erxian has positive effects on treating osteoporosis.

[Effect of puerarin and ligustrazine on cultured hippocampal neurons injury induced by Abeta25-35].

OBJECTIVE: To investigate the changes of MDA, SOD, LDH of cultured hippocampal neurons injury induced by amyloid-beta protein (Abeta 25-35) and the protective effect of puerarin and ligustrazine. METHOD: Primary hippocampal neurons were cultured and induced by Abeta 25-35. The concentrations of MDA, SOD and LDH in cultured hippocampal neurons were measured after exposed to Abeta 25-35, puerarin and ligustrazine. RESULT: The Alzheimer disease (AD) model was successfully established in cultured hippocampal neurons. AD group has remarkably increased MDA and LDH level, and decreased SOD level, Piracetan group and combined application group of have remarkably decreased MDA and LDH level and increased SOD level, compared with AD group (P < 0.01). Ligustrazine together with puerarin group has remarkably decreased MDA and LDH level and increased SOD level, compared with ligustrazine group and puerarin group (P < 0.05). CONCLUSION: Abeta 25-35 can induce cultured hippocampal neurons injury, combined application of ligustrazine, and puerarin can alleviate the injury.

Artificial neural network based model for cardiovascular risk stratification in hypertension.

This study was to develop an objective method to stratify cardiovascular risk in hypertension. Stratification for cardiovascular risk is crucial in deciding treatment strategy for hypertension but has yielded undesirable results in clinic due to its low accuracy which is caused by physicians' subjective experience and the uncertainty of patients' statements. Our model proposed herein overcomes these disadvantages by applying artificial neural network based on a classic back propagation net. The model input is derived from the clinical investigation. The target output is the stratification level of total cardiovascular risk, which is learned from the guidelines of hypertension treatment. Study in 348 normotensive and hypertensive subjects showed that the results of model stratification are consistent with the standard stratification suggested by hypertension guidelines in 81.61% cases. The results confirm the accuracy of the model and demonstrate its ability in risk evaluation for hypertension.

Investigation of beat-to-beat cardiovascular activity of rats by radio telemetry.

This paper was aimed to apply telemetry technology to investigate the cardiovascular activity of rats. A subminiature radio transducer was implanted in the body of rat to measure beat to beat blood pressure, ECG, body temperature, as well as the activity of rat continuously. Mathematic tools were developed to extract beat to beat cardiovascular parameters. Accordingly, spectral analysis of blood pressure variability and heart rate variability was performed to analyze cardiovascular activity in both normotensive and hypertensive rats. New indices were also established to assess the fluctuation of blood pressure of hypertensive rats and thus the effect of anti-hypertensive medication. The ratio of low frequency power to high frequency power in heart rate variability of normotensive rats was much lower than that of hypertensive rats. In hypertensive rats, the blood pressure variability demonstrated significant increase. Furthermore, the circadian rhythm of blood pressure and heart rate variability also altered in hypertensive rats. After the treatment, the blood pressure of hypertensive rats dropped significantly. Meanwhile, the developed indices, such as 24 h smoothness index were consistent with the behavior of blood pressure satisfactorily. The results suggest that the developed methods are powerful in studying cardiovascular system as well as evaluating the effects of antihypertensive medication objectively.

[Establishment of a system for measuring blood flow velocity of rat microvessel using dark background fluorescent image analysis method].

Autologous red blood cells (RBC) labeled with fluorescence were immitted into microvessel of SD rat and observed under microscope. The movement of each individual labeled RBC was recorded by microscope video camera system. The recorded videotape is replayed to sample dark background fluorescent images through frame grabber. Sampled frame images were separated into odd and even field sequence images. Then these sequence images were analyzed to get the flow rate. The error between the actual flow velocity value and the flow velocity value of fluorescent globules in the chamber measured under the same system was below 7%. The upper limit was 9.6 mm/s. There are no obvious differences (P > 0.05). This system has been applied in the research of rat microcirculatory disturbance, and the temporal flow rate change in microvessel was obtained.

The Neuroprotection of puerarin against cerebral ischemia is associated with the prevention of apoptosis in rats.

Previous work has shown that puerarin (Pur), extracted from the dried root of Pueraria lobata (Wild) Ohwi, increases cerebral blood flow in dogs and attenuates cerebral and spinal cord injury resulting from ischemia and reperfusion in rats and rabbits. The present study further demonstrates the neuroprotective effects of Pur on cerebral ischemic injury in rats and the mechanisms underlying the protective effects. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAo) for 50 min followed by reperfusion for 24 h. Pur (50, 100 mg/kg, i.p) was administered at the onset of MCAo. Twenty-four hours after reperfusion, neurological deficits were evaluated in Pur- and vehicle-treated rats. The infarct volume and edema ratios were assessed from stained brain slices. The results showed that Pur (100 mg/kg) markedly decreased the infarct volume by 34 % ( P < 0.01) in cerebral cortex and improved the neurological functions ( P < 0.05) after MCAo. Furthermore, flow cytometric analysis of annexin-V and PI labeling cells showed that the percentages of apoptosis and necrosis in the dorsolateral cortex were significantly reduced by 38.6 % and 28.5 % ( P < 0.01 and P < 0.05) following treatment with Pur (100 mg/kg) in MCAo rats. Caspase-3 activity, a biochemical marker of apoptosis, was significantly inhibited after treatment with Pur in the dorsolateral cortex. In agreement with this result, the expression of the X-chromosome-linked inhibitor of apoptosis protein (XIAP) was obviously up-regulated after administration of Pur (100 mg/kg), while caspase-3 gene was down-regulated in the dorsolateral cortex. These results suggest that the neuroprotection of puerarin against cerebral ischemia is associated with anti-apoptosis.

Application of cell engineering of herbal Medicine treating bone resorption of osteoclasts.

UNLABELLED: To investigate application of cell engineering in herbal Medicine treating bone resorption. STUDY DESIGN: the bone marrow cells were isolated from 5 week-old SD rats and induced by 1,25(OH)2D3. Firstly, Morphological assay, cells were fixed, stained by tartrate-resistant acid phosphatase (TRAP) and observed with the fluorescence micrograph. F-actin rings of OCLs were labled using Bodipy FL Phallacidin and PI, and observed with the laser scanning confocal microscope, then also showed the ultrastructure of them with the scanning electron microscope. Secondly, bone pits were observed after bone slices were stained by paraosaniline hydrochloride. Thirdly, the number of TRAP (+) cells with above two nuclei was counted, and TRAP activity of OCLs was examined with TRAP kit. In addition, effects of Traditional Chinese Medicine, such as Oral Liquid of Guiluerxian, on the differentiation and function of OCLs were observed. Results indicated that application of cell engineering made it possible to observe vividly the morphology of osteoclasts, study its function and mechanism underlying bone resorption.

A study of the cardioprotective effect of breviscapine during hypoxia of cardiomyocytes.

Breviscapine is a flavonoid extracted from Erigeron breviscapus. Hand.-Mazz, and it has been reported that breviscapine can activate K+ channels and block Ca2+ channels. In this paper, we studied the cardioprotective effects of breviscapine on electrocardiogram (ECG) changes (ST-segment elevation), infarction size in dog heart subjected to myocardial infarction caused by left coronary artery ligation and lactate dehydrogenase (LDH) leakage, changes of intracellular free Ca2+ levels, apoptosis and necrosis in cultured neonatal rat cardiomyocytes subjected to hypoxia. Additionally, the effect of breviscapine on myocardial oxygen consumption was detected in dog myocardium in vitro. The results showed that breviscapine treatment (1 mg/kg, 2 mg/kg and 4 mg/kg) significantly reduced ST-segment elevation and infarction size in hearts subjected to myocardial infarction, that breviscapine treatment (14.29 microg/mL, 28.57 microg/mL and 57.14 microg/mL) significantly decreased oxygen consumption in myocardium, and that breviscapine treatment (5 microg/mL, 10 microg/mL and 20 microg/mL) significantly reduced LDH leakage, intracellular free Ca2+ levels, apoptosis and necrosis in cardiomyocytes subjected to hypoxia. In conclusion, the present study indicates that breviscapine is in favor of myocardial protection.

[The effect of recombinant human erythropoietin on postoperative anemia in orthognathic patients].

PURPOSE: To observe the effect of rhEPO on postoperative anemia in orthognathic patients. METHODS: 31 patients had 500-1200 ml blood loss during orthognathic operation, who were divided into two groups randomly, the experiment group and the control group. The patients in the experiment group received rhEPO 6000IU subcutaneously for 3 times in a week and Ferrost sulfatis Et vitamini-medtech 1 tablet per day via oral administration for 12 days after operation, while the patients in the control group only received the same dose of Ferrost sulfatis Et vitamini-medtech. The loss of blood of the patients during operation were estimated and recorded. Their Hb and Hct were mensured before operation, and in the first, third, seventh-twelfth day after operation. RESULTS: In the twelfth day after operation, the Hb and Hct of the patients in the experiment group had a significantly higher increase than that in the control group (P<0.05). CONCLUSIONS: rhEPO combined Ferrost sulfatis Et vitamini-medtech are suitable to apply in orthognathic patients with anemia after operation, which may effectively accelerate the recovery of their anemia, and avoid transfusion of blood.