Serum 25 hydroxyvitamin D in non-scarring alopecia: A systematic review and meta-analysis.

INTRODUCTION: Non-scarring alopecia mainly includes androgenetic alopecia (AGA), female pattern hair loss (FPHL), alopecia areata (AA), telogen effluvium (TE), anagen effluvium (AE) and so on. Many studies had investigated the serum 25-hydroxyvitamin D level and vitamin D deficiency of patients with these diseases, but opinions varied, and no conclusion was reached. METHODS: Relevant articles were retrieved through PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other databases. Serum 25-hydroxyvitamin D [25(OH) D] levels and vitamin D deficiency were used as our primary outcome. The odds ratio (OR) and the standardized mean difference (SMD) with 95% confidence interval were both examined for vitamin D deficiency and levels. RESULTS: Our meta-analysis had included a total of 3374 non-scarring alopecia patients and 7296 healthy controls from 23 studies through the inclusion criteria and exclusion criteria. We found non-scarring alopecia had decreased serum 25(OH)D level (WMD -7.29; 95% CI -9.21, -5.38) and increased vitamin D deficiency incidence (OR 3.11 95% CI 2.29, 4.22), compared with healthy controls. This meta-analysis chose to conduct random-effect model and subgroup analysis, because of the high heterogeneity (serum 25(OH)D level: I2 = 95%, vitamin D deficiency: I2 = 0%). CONCLUSION: Patients with non-scarring alopecia (including AA, FPHL, AGA and TE) have insufficient serum level of 25(OH)D and increased incidence of vitamin D deficiency. Vitamin D supplementation and monitoring for vitamin D deficiency may be helpful in treating non-scarring alopecia.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

New perspective on the immunomodulatory activity of ginsenosides: Focus on effective therapies for post-COVID-19.

More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10-60% of patients are expected to exhibit "post-COVID-19 symptoms," which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase blood oxygen saturation. Ginsenosides are the main active components of ginseng. In this review, we summarize the multiple ways in which ginsenosides affect post-COVID-19 symptoms, including inhibition of lipopolysaccharide, tumor necrosis factor signaling, modulation of chemokine receptors and inflammasome activation, induction of macrophage polarization, effects on Toll-like receptors, nuclear factor kappa-B, the mitogen-activated protein kinase pathway, lymphocytes, intestinal flora, and epigenetic regulation. Ginsenosides affect virus-mediated tissue damage, local or systemic inflammation, immune modulation, and other links, thus alleviating respiratory and pulmonary symptoms, reducing the cardiac burden, protecting the nervous system, and providing new ideas for the rehabilitation of patients with post-COVID-19 symptoms. Furthermore, we analyzed its role in strengthening body resistance to eliminate pathogenic factors from the perspective of ginseng-epidemic disease and highlighted the challenges in clinical applications. However, the benefit of ginsenosides in modulating organismal imbalance post-COVID-19 needs to be further evaluated to better validate the pharmacological mechanisms associated with their traditional efficacy and to determine their role in individualized therapy.

Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer.

Background: Docetaxel (DCT) is widely used in clinical practice, but the drug resistance of breast cancer patients has become an important reason to limit its clinical efficacy. Chan'su is a commonly used traditional Chinese medicine for the treatment of breast cancer. Bufalin (BUF) is a bioactive polyhydroxy steroid extracted from chan'su and has strong antitumor activity, but there are few studies on reversing drug resistance in breast cancer. The aim of this study is to determine whether BUF can reverse the drug resistance to DCT and restore efficacy in breast cancer. Methodology: The reversal index of BUF was detected by Cell Counting Kit-8 (CCK-8) assays. The effects of BUF on enhancing the apoptosis of DCT were detected by flow cytometry and Western Blot (WB), and the main differential expression levels of sensitive and resistant strains were detected by high-throughput sequencing. Rhodamine 123 assay, WB and ATP Binding Cassette Subfamily B Member 1 (ABCB1) ATPase activity experiments were used to detect the effect of BUF on ABCB1. The nude mouse orthotopic model was constructed to investigate the reversal effect of BUF on DCT resistance in vivo. Results: With BUF intervention, the sensitivity of drug-resistant cell lines to DCT was increased. BUF can inhibit the expression of ABCB1 protein, increase the drug accumulation of DCT in drug-resistant strains, and reduce the ATPase activity of ABCB1. Animal experiments show that BUF can inhibit the growth of drug-resistant tumors in an orthotopic model of breast cancer and decrease the expression of ABCB1. Conclusion: BUF can reverse ABCB1-mediated docetaxel resistance in breast cancer.

Sperm mitochondrial DNA copy number mediates the association between seminal plasma selenium concentrations and semen quality among healthy men.

Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.

Glucosamine inhibits extracellular matrix accumulation in experimental diabetic nephropathy.

Introduction: Glucosamine, the intermediate metabolite of the hexosamine biosynthesis pathway (HBP), is widely used as a supplementary drug in patients with osteoarthritis. However, its consequences in such patients concomitantly suffering from diabetic nephropathy is unknown. Methods: The aim of the study was to investigate the effect of exogenous administration of glucosamine in the diabetic kidney. A mouse model of streptozotocin-induced diabetic nephropathy in vivo and cultured endothelial cells in vitro were used in the study. The mice were treated with glucosamine for 6 months. Renal function was evaluated by metabolic cage, and histology of the kidney was estimated by periodic acid-schiff (PAS) staining. The expression of related genes was assessed by real-time PCR, immunofluorescence staining, immunoblotting and ELISA. Results: There was no significant difference in urinary albumin secretion, relative kidney weight, or creatinine clearance between the groups treated with glucosamine and controls. Assessment of the kidney demonstrated reduction in mesangial expansion and fibronectin expression in the diabetic glomeruli treated with glucosamine. Glucosamine treatment significantly decreased α-smooth muscle actin (α-SMA) protein expression in both diabetic and control kidneys, whereas the expression of other fibrosis-related genes and inflammatory factors was unaltered. Moreover, α-SMA colocalized with the endothelial marker CD31 in the diabetic and control kidneys, and glucosamine reduced α-SMA+ ECs in the diabetic glomeruli. In addition, glucosamine suppressed α-SMA expression in endothelial cells treated with or without high glucose. Discussion: In summary, this is the first report to show that glucosamine reduces mesangial expansion and inhibits endothelial-mesenchymal transition in diabetic nephropathy. The underlying mechanisms need to be further investigated.

Environmental metal exposure, seminal plasma metabolome and semen quality: Evidence from Chinese reproductive-aged men.

Environmental metal exposure has been associated with decreasing semen quality, but the effects of multiple metal exposure on seminal plasma metabolome remain obscure. In this study, semen and repeated urine samples from 551 volunteers were collected in Wuhan City. Heavy metals and trace elements were measured using inductively coupled plasma mass spectrometer, and seminal plasma metabolomes were acquired using liquid chromatography coupled with high-resolution mass spectrometry. Weighted gene co-expression network analysis showed more than half of the seminal plasma metals were associated with specific metabolite modules, whereas only a few urine metals presented weak associations, indicating that seminal plasma may be an ideal biological sample for male reproductive biomarker discovery and exposure risk assessment. Seminal plasma zinc (Zn) and selenium (Se) concentrations were significantly associated with 22 metabolites (e.g., glycerophospholipids, acyl-carnitines and amino acid derivatives). Among these metabolites, acyl-carnitines were positively associated with semen quality and sperm concentration. Moreover, acyl-carnitines were associated with both Zn and Se exposure, indicating the potential role of carnitine pathway in their toxicity mechanism. Our findings suggest that seminal plasma metabolome connects Zn and Se exposure and sperm concentrations in Chinese men of reproductive age.

Association between tea consumption and semen quality among 1385 healthy Chinese men.

Information on the association between tea drinking and semen quality is limited. Little is reported on whether tea drinking is benefit to sperm quality. This cross-sectional and longitudinal study was conducted between April 2017 and July 2018. Participants were healthy men who were screened as potential sperm donors recruited at the Hubei Province Human Sperm Bank of China. A structured questionnaires containing sociodemographic information, daily habits, sperm collection-related information was completed for each participant at interview. Repeated semen samples were taken to examine the sperm parameters, including sperm volume, sperm concentration, sperm count, progressive motility, and total motility. A total of 1385 men with 6466 sperm samples were included in this study. Two groups were compared: tea drinking men (389, 28.1%) and non-tea drinking men (996, 71.9%). Compared with subjects who never drink tea, the analyses showed that sperm concentration and total sperm count were higher in tea-consuming subjects. A 10-year period or more duration of tea drinking significantly increased semen concentrations by 16.27% (P < 0.05). Sperm concentration was increased in subjects with a frequency of tea drinking of 3 days or more per week (P < 0.05) or, among men who were occasional alcohol drinkers, when tea concentration was weak (P < 0.05). No evidence of trend effects (P for trend > 0.05) or interaction effects (P for interaction > 0.05) between tea consumption and sperm quality, respectively. Our findings provide evidence that tea drinking may improve male reproductive health. Long-term, frequent, weak tea drinking tends to increase sperm quality among men with low BMI or health-related behaviors like smoking or alcohol intake.

Effect of "Natural Polypill", Xuezhikang on Serum Cholesterol Metabolism Markers in Early Menopausal Women with Hypercholesterolemia.

OBJECTIVE: To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS: Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."

[Active components and action mechanism of Shenmai Injection in treatment of atrial fibrillation based on network pharmacology and molecular docking].

This study aims to explore the active components and molecular mechanism of Shenmai Injection in the treatment of atrial fibrillation(AF) based on the application of network pharmacology and molecular docking technology. The chemical components of single herbs of Shenmai Injection were collected from TCMSP and TCMID, with the standard chemical name and PubChem CID(referred to as CID) obtained from PubChem database. The active components were screened using SwissADME, and their targets were predicted using SwissTargetPrediction. Targets related to AF treatment were identified using GeneCards, OMIM, and other databases. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. The single herb-active component-potential target network was constructed using Cytoscape, and the clusterProfiler R function package was used to perform the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The protein-protein interaction(PPI) network of intersection targets was generated based on the STRING database. The hub target protein was identified by visualization using Cytoscape, and then docked to its reverse-selected active components. The analysis showed that there were 65 active components with 681 corresponding targets in Shenmai Injection, 2 798 targets related to AF treatment, and 235 intersection targets involving 2 549 GO functions and 153 KEGG pathways. Finally, hub target proteins, including RAC-alpha serine/threonine-protein kinase(AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA), and estrogen receptor 1(ESR1), were screened out by PPI network visualization. The molecular docking was performed for 39 active components screened out in reverse, among which 30 active components de-monstrated high affinity. Among them, homoisoflavanoids CID 10871974, CID 5319742, and CID 10361149 had stronger affinity docking with AKT1. This study preliminarily indicates that Shenmai Injection treats AF through multiple components, multiple targets, and multiple pathways. Homoisoflavonoids of Ophiopogon japonicus are its important active components, which target AKT1 to regulate metabolism, inflammation, and apoptosis in AF treatment.

Identifying windows of susceptibility to essential elements for semen quality among 1428 healthy men screened as potential sperm donors.

BACKGROUND: Essential elements such as iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), and molybdenum (Mo) are necessary for reproductive health. However, their associations with human semen quality remain inconclusive. OBJECTIVES: To investigate the associations of urinary Fe, Co, Cu, Zn, Se, Rb, Sr, and Mo concentrations with semen quality in healthy men screened as potential sperm donors and identify critical windows of susceptibility. METHODS: 1428 healthy men provided 3766 urine and 6527 semen samples, which were measured for urinary essential element concentrations and sperm quality parameters, respectively. Linear mixed models and cubic spline curves were used to evaluate associations between urinary essential elements and semen quality. Multiple informant models were used to identify potential critical windows of susceptibility. RESULTS: Linear mixed models and cubic spline curves showed positive dose-response relationships between urinary Zn and sperm concentration and total count and between urinary Mo and total sperm count [all False Discovery Rate (FDR) adjusted p-value for trend < 0.05]. In the multiple-element linear mixed models, the men in the highest versus lowest quartiles of urinary Zn and Mo had a higher sperm concentration of 17.5% (95% CI: 2.8%, 34.2%; p-value for trend = 0.006) and total sperm count of 18.3% (95% CI: 1.4%, 38.0%; p-value for trend = 0.027), respectively. Urinary Zn was also positively associated with total sperm count in a dose-dependent manner (p-value for trend = 0.036), though the percentile difference in total sperm count between men in the highest and lowest quartile was not statistically significant (16.4%, 95% CI: -1.7%, 37.9%). These associations appeared to be stronger when urinary Zn and Mo were measured at 0-9 days before the date of semen examination (i.e., corresponding to epididymal storage). CONCLUSIONS: Higher urinary Zn and Mo, particularly during the period of epididymal storage, were associated with greater sperm production.

Silver-decorated mesostructured cellular silica foams as excellent antibacterial hemostatic agents for rapid and effective treatment of hemorrhage.

Uncontrolled bleeding, such as deep, narrow or irregular wound hemorrhage, has been a major cause of death in peacetime and wartime. Besides, traditional hemostatic agents are lack of antibacterial properties, which could not provide effective protection on open wound. In this paper, a novel antibacterial hemostatic agent composed of mesostructured cellular silica foams (MCF) decorated with silver ions (MCF-Ag) was synthesized by hydrothermal method. Hemorrhage wound infected with Escherichia coli was applied to evaluate its antibacterial and hemostatic performance both in vitro and in vivo. Both MCF and MCF-Ag showed excellent hemostasis in vitro and in vivo. The MCF-Ag demonstrated significant antibacterial effect. By contrast, no obvious antibacterial effect was observed from the MCF. The above results demonstrate that the MCF-Ag is an excellent antibacterial hemostatic agent with splendid water absorption and antibacterial capacity.

Onion Epithelial Membrane Scaffolds Transfer Corneal Epithelial Layers in Reconstruction Surgery.

Plants and their extracts have been used especially in China for more than ten centuries for preventing and treating disease. However, there are only few reports describing their use in animal cell culture and tissue transplantation. In this study, onion epithelial membranes (OEM) is used as scaffolds to support cultures of a variety of cells such as fibroblasts and epithelial cells notably; they maintain the phenotypic characteristics of corneal epithelial cells. This improvement includes preservation of the proliferative potential and stemness of rabbit corneal epithelial cells (RCECs). Such an outcome suggests that this cost-effective technology warrants further evaluation to determine if OEM is a viable candidate for use as scaffolds in corneal epithelial transplantation surgery. To test this possibility, rabbit corneal epithelial cells expanded on OEM are transplanted to treat corneal epithelial defects in limbal stem cell deficient rabbits. This procedure is successful because it shortens the time required for wound healing to restore losses in corneal epithelial integrity, and forms a more compact and stratified epithelium framework than the untreated group. Ultimately, should they be proven to be effective in other relevant animal model systems, their usefulness for treating wounds in a clinical setting warrants consideration.

[Effect of scalp acupuncture stimulation on expression of pentraxin 3 in striatum in acute ische-mic cerebrovascular disease rats].

OBJECTIVE: To observe the influence of scalp-acupuncture on the expression of pentraxin 3 (PTX3), Interleukin (IL)-1ß, zonula occludens-1(ZO-1) mRNA and Occludin mRNA in striatum in acute ischemic cerebrovascular disease (AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to control, model, IL-1Ra and IL-1Ra+scalp-acupuncture groups (n=12 rats in each group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the IL-1Ra group and IL-1Ra+scalp-acupuncture group received intraperitoneal injection of IL-1Ra (0.05 mg·kg-1·d-1), once daily for 6 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 6 days for rats in IL-1Ra+scalp-acupuncture group. Before and after intervention, the neurologic deficit score (NDS) was evalua-ted according to Longa's method. The expression of striatum PTX3 and IL-1ß was detected by immunohistochemistry, and ZO-1 mRNA and Occludin mRNA in the striatum tissue were detected by fluorescence quantitative real-time PCR. The Evans Blue (EB) tracer method was used to monitor the degree of blood-brain barrier (BBB) damage. RESULTS: Following modeling, the NDS, EB content and the expression of PTX3 and IL-1ß in the striatum tissue were significantly increased, and the ZO-1 mRNA and Occludin mRNA expression was considerably decreased in the model group compared with the control group (P<0.05). After the interventions and compared with the model group, the NDS, EB content in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra group were significantly down-regulated (P<0.05), while the striatum ZO-1 mRNA and Occludin mRNA expression in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra+scalp acupuncture group were obviously up-regulated (P<0.05), and the expression of IL-1ß was obviously down-regulated in the IL-1Ra+scalp acupuncture group (P<0.05) rather than in the IL-1Ra group (P>0.05). The effects of scalp acupuncture combined with IL-1Ra were obviously superior to that of IL-1Ra in down-regulating NDS, EB content and IL-1ß expression level, and in up-regulating PTX3, ZO-1 mRNA and Occludin mRNA expression levels (P<0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce the degree of BBB injury in AICD rats, which may be associated with its function in up-regulating the expression of PTX3 and in promoting the expression of ZO-1 mRNA and Occludin mRNA.

[ZHENG' Guo-Yan-Re needling technique for diabetic fundus hemorrhage].

OBJECTIVE: To observe the clinical effect of ZHENG ' Guo-Yan-Re needling technique for diabetic fundus hemorrhage. METHODS: With before-after study design, 34 patients with diabetic eyeground hemorrhage were treated with basic treatment (oral administration of antidiabetic medication or insulin injections to ensure blood glucose in the normal range); in addition, acupuncture was given at bilateral Fengchi (GB 20), Taiyang (EX-HN 5), Jingming (BL 1), Cuanzhu (BL 2), Sanyinjiao (SP 6) and Hegu (LI 4). The ZHENG ' Guo-Yan-Re needling technique was applied at Fengchi (GB 20); the heat reinforcing needling technique was applied at Taiyang (EX-HN 5); the slow needle insertion technique was applied at Jingming (BL 1); and the Xique-Dengmei needling technique was applied at Cuanzhu (BL 2); the neutral supplementation and draining method was applied at remaining acupoints. The acupuncture was given once a day, 6 times as one course, and totally 4 courses were given with an interval of 1 day between courses. The follow-up visit was 6 months after treatment. The TCM symptom scores, fundus examination results and vision improvement were observed before and after treatment, and the effect was observed. RESULTS: Compared before treatment, the visual acuity, TCM symptom scores, fundus microaneurysm and hemorrhage points in 34 patients (68 eyes) were significantly improved after treatment (P<0.05). The total effective rate was 88.2% (60/68) after treatment; at follow-up visit, the visual acuity, TCM symptom scores and fundus pathological changes were all improved (P<0.05) and stable at the post-treatment level (P>0.05). CONCLUSION: ZHENG ' Guo-Yan-Re needling technique could improve symptoms, promote the absorption of fundus hemorrhage, and improve vision in patients with diabetic fundus hemorrhage.

Reproducibility of essential elements chromium, manganese, iron, zinc and selenium in spot samples, first-morning voids and 24-h collections from healthy adult men.

Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals' 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01-0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals' long-term exposures.

Glucosamine sulphate-loaded distearoyl phosphocholine liposomes for osteoarthritis treatment: combination of sustained drug release and improved lubrication.

Osteoarthritis (OA) is a chronic joint disease resulting from joint inflammation and damage. In this study, we employed a boundary lubricant known as a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposome for loading of an anti-inflammatory drug d-glucosamine sulphate (GAS) to construct a treatment strategy allowing for sustained anti-inflammation and reduced damage. This kind of drug-loaded nanocarrier integrates the anti-inflammatory effect of the GAS and the lubrication ability of DSPC liposomes without the involvement of complex synthesis processes leading to easier popularization. Our experimental results indicated that the GAS-loaded DSPC liposomes could release GAS in a sustained manner while providing good lubrication in pure water (H2O) and phosphate buffered saline (PBS). Moreover, the GAS-loaded DSPC liposomes prepared at a 2 : 8 molar ratio in PBS exhibited a greater entrapment efficiency, lower GAS release rate and smaller friction coefficient as compared to those prepared in H2O. The superiority of the drug release and lubrication ability achieved with the GAS-loaded DSPC liposomes in PBS were elucidated on the basis of salt-induced enhancement in liposomal stability and hydration lubrication by the hydrated salt ions. Such GAS release accelerated the viability and proliferation of primary mouse chondrocytes while also providing the anti-inflammatory and chondroprotective potential for tumor necrosis factor (TNF-α) induced chondrocyte degeneration through the down-regulation of pro-inflammatory cytokines, pain related gene and catabolic proteases, as well as the up-regulation of anabolic components. We envision that the GAS-loaded DSPC liposomes could represent a promising new strategy for clinical treatment of OA in the future.

The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and NASH when fed a Western diet supplemented with fructose.

BACKGROUND: Metabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH. METHODS: Male FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated. RESULTS: Compared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4-2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels. CONCLUSION: WDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation.

Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication.

Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC⁻MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.