Konjac glucomannan attenuate high-fat diet-fed obesity through enhancing ß-adrenergic-mediated thermogenesis in inguinal white adipose tissue in mice.

Konjac glucomannan (KGM) has been reported to prevent high-fat diet-induced obesity, and we study investigated whether dietary supplementation with KGM can prevent obesity by increasing energy expenditure in inguinal white adipose tissue (iWAT) of high-fat diet (HF) -fed mice. Weaned mice fed the control diet (Con), HF, or HF plus KGM (8%, w/w, HFK) were divided into three groups. The results showed that 10-week supplementation with KGM significantly reduced partial adipose tissue weight and body weight, and improved glucose tolerance. Compared to the HF group, plasma lipid concentrations in the HFK group were greatly decreased to the control level. Moreover, transcriptomic research has shown that genes that are mainly associated with energy and lipid metabolism are significantly altered in iWAT. Mechanistically, KGM stimulated thermogenesis by promoting the expression of uncoupling protein-1 (UCP1) and the ß3-adrenergic receptor (ADR3ß). Taken together, our results suggest that dietary supplementation with konjac glucomannan can effectively alleviate obesity induced by a high-fat diet by activating ADR3ß-mediated iWAT thermogenesis. Dietary supplementation with KGM can effectively alleviate high fat diet- induced obesity mice by via activating ADR3ß-mediated thermogenesis of iWAT.

Identification of chemical constituents in pomegranate seeds based on ultra-high-performance supercritical fluid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Pomegranate seeds are a potential source of bioactive compounds. Nonetheless, most pomegranate seeds are discarded in the food processing industry, likely due to the lack of convincing data on their component analysis. METHODS: To reveal the main chemical constituents of pomegranate seeds, a reliable and sensitive method based on ultra-high-performance supercritical fluid chromatography coupled with electrospray ionization and quadrupole time-of-flight mass spectrometry (MS) was developed. A time-dependent MSE data acquisition mode was applied to acquire the mass spectrometric data. The chemical constituents were identified by an automatic retrieval of a traditional Chinese medicine library and relevant literature. RESULTS: A total number of 59 compounds, including fatty acids, sterols, vitamins, cerebrosides, phospholipids, flavonoids, phenylpropanoids, and others, were tentatively identified. Their possible fragmentation pathways and characteristic ions were proposed and elucidated. CONCLUSIONS: The findings of this study, along with the developed methodology, could provide a reference for basic research on the pharmacodynamic substances of pomegranate seeds and shed light on their potential nutritional and therapeutic applications in the future.

[Explore antioxidant quality markers of Hippophae tibetana based on "dry-method + wet-method" technology].

The cross combination of dry-method(network pharmacology analysis) and wet-method(high-resolution mass spectro-metry with antioxidation experiment) was used to predict antioxidant quality markers(Q-markers) of Hippophae tibetana. Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was developed to rapidly separate and identify the chemical constituents in H. tibetana. Then in DPPH free radicals and superoxide anion scavenging experiment, the antioxidant activity of the four different polar parts with extracts of petroleumether, ethyl acetate, n-butanol and water was evaluated. Network pharmacology method was used for functional enrichment and pathway analysis to screen antioxidant-related components and preliminarily explain the mechanism of action. On this basis, multi-source information was integrated to predict the antioxidant Q-markers. The results showed that 51 components in H. tibetana were identified, including 18 flavonoids, 14 terpenoids, 6 alkaloids, 4 coumarins and phenylpropanoids, 3 volatile components and 2 polyphenols. The antioxidant capacity of different fractions: ethyl acetate > n-butanol > water > petroleum ether. The medicine mainly acted on PI3 K-Akt and FoxO signaling pathways to perform antioxidant effects through flavonoids such as quercetin, luteolin and kaempferol. According to the results of dry-method and wet-method, quercetin, luteolin and kaempferol, the representatives of poly-hydroxy flavone, may be the antioxidant Q-markers of H. tibetana. In this study, with the antioxidant Q-markers of H. tibetana as an example, an investigation model of predicting Q-marker was discussed based on the ternary system of composition, function and informatics, providing a scientific basis for the establishment of quality evaluation standards for H. tibetana.

Safety and Efficacy of Therapeutic Erythrocytapheresis Treatment in Chronic Mountain Sickness Patients in Shigatse, Tibet, China.

BACKGROUND Therapeutic erythrocytapheresis (TEA) is a medical technology that separates erythrocytes from whole blood and has been used in various hematological conditions. However, reports on the use of TEA to treat chronic mountain sickness (CMS) are lacking. The aim of the present study was to evaluate the efficacy, safety, and use of TEA in treatment of CMS. MATERIAL AND METHODS A total of 32 patients living in the Shigatse area of Tibet (altitude 4000 m) who had CMS were treated with TEA. Clinical data, CMS score, Borg dyspnea score, 6-min walking test score, and NYHA classification values were collected prior to and after TEA therapy. RESULTS TEA treatment significantly increased SpO2 (93.8±2.6 vs. 80.5±5.8%, P<0.001) and decreased red blood cell (5.77±0.70 vs. 7.48±0.67×10¹²/L, P<0.001), hematocrit (53.8±5.6 vs. 69.2±4.8%, P<0.001) and hemoglobin (178±16 vs. 236±14 g/L, P<0.001). Significantly lower systolic and diastolic blood pressure were also noted (P<0.001). Echocardiography showed higher left ventricle diameter (4.6±0.4 vs. 4.4±0.5 cm, P<0.01). TEA markedly decreased CMS scores (0.45±0.85 vs. 7.58±2.31, P<0.001), Borg dyspnea scale scores (0.48±0.73 vs. 0.88±0.81, P<0.001), and NYHA classification scores (P<0.05). Additionally, there was marked improvement in the 6-min walking test scores (578.5±83.1 vs. 550.4±79.0 m, P<0.001). The procedure was well tolerated, with no complications. CONCLUSIONS Our novel approach of treating CMS patients with TEA safely and effectively reduced erythrocytosis, which remains a fundamental challenge in CMS patients.

Efficacy and Safety of Single- or Double-Drug Antidiabetic Regimens in the Treatment of Type 2 Diabetes Mellitus: A Network Meta-Analysis.

A network meta-analysis was performed in order to compare the efficacy and safety of single- or double-drug antidiabetic regimens in the treatment of type 2 diabetes mellitus (T2DM). PubMed and Cochrane Library searches were conducted since inception to February 2017. Randomized controlled trials (RCTs) of different antidiabetic regimens in the treatment of T2DM were included in this study. Direct and indirect evidences were combined to calculate the odds ratio (OR) or weighted mean difference (WMD) and its 95% confidence interval (95%CI), and in order to draw the surface under the cumulative ranking curves (SUCRA). A total of 19 RCTs meeting our inclusion criteria were finally incorporated into our network meta-analysis, including 19 single- or double-drug antidiabetic regimens. The network meta-analysis showed that the anti-hyperglycemic effects of Sitagliptin + Metformin, Empagliflozin + Metformin, Exenatide + Metformin, Vildagliptin + Metformin, Taspoglutide + Metformin, and Pioglitazone + Metformin were better than individual Metformin regimens. Dulaglutide + Metformin and Taspoglutide + Metformin regimens were comparatively less safe than individual Metformin regimens. The cluster ranking analysis based on SUCRA values suggested that Taspoglutide + Metformin regimens had best efficacy and worst safety among the different therapy regimens. Our data confirmed previous observations and suggested that Taspoglutide + Metformin regimen may have better efficacy for the treatment of T2DM among 19 therapy regimens, while its incidence of adverse events was relatively higher. J. Cell. Biochem. 118: 4536-4547, 2017. © 2017 Wiley Periodicals, Inc.

[A strategy for identifying six species of Sect.Cruciata(Gentiana) in Gansu using DNA barcode sequences].

Located in the transition zone between the Qinghai-Tibet Plateau and the Loess Plateau, Gansu province is one of the distribution centers of Sect. Cruciata, Gentiana (Gentianaceae) in China. Six species in the section, G. crassicaulis, G. straminea, G. siphonantha, G. officinalis, G. dahurica and G . macrophylla, are native to Gansu. In this paper, samples of 6 species and Halenia elliptica (outgroup) were collected. Nuclear DNA ITS, chloroplast DNA matK, rbcL, rpoC1, trnL (UAA) intron, psbA-trnH, atpB-rbcL, trnS (GCU)-trnG (UCC), rpl20-rps12 and trnL (UAA)-trnF (GAA) were sequenced from these samples. Based on the sequence analyses, high intragenomic polymorphisms were detected in ITS regions of G. crassicaulis, G. straminea, G. siphonantha, G. officinalis and G. dahurica, and they showed incomplete concerted evolution. A methodological study to identifying such close-related species as G. macrophylla, G. officinalis and G. dahurica was carried out based on the special genotypes. The results showed that 7 cp DNA sequence fragments could be used to identify G. crassicaulis, G. straminea and G. siphonantha. With nr ITS genotype II,III and IV of G. dahurica, the species can be distinguished from the close-related G. officinalis using 12 cloned sequences in a sample (with statistical significance).The cp DNA sequences of G. macrophylla were classified into two genotypes, and with genotype II, the species can be distinguished from the close-related G. officinalis and G. dahurica using 6 test samples each(with statistical significance). Furthermore, DNA barcode sequences were determined for all 6 species in Gansu. Also, the studies provide some basic data for analyses of genetic diversity and identification of Gentiana species.

[DNA-based identification of Gentiana robusta and related species].

The alpine plant Gentiana robusta is an endemic species to the Sino-Himalayan subregion. Also, it is one of the original plants used as traditional Tibetan medicine Jie-Ji. We sequence the nuclear ribosomal internal transcribed spacer (ITS) regions, matK, rbcL, rpoC1, trnL (UAA), psbA-trnH, atpB-rbcL, trnS( GCU)-trnG(UCC), rpl20-rps12, trnL(UAA)-trnF( GAA) fragments of cp DNA in both G. robusta and such relative species as G. straminea, G. crassicaulis and G. waltonii. With Halenia elliptica as the outgroup, molecular systematic analysis reveals that G. robusta is a natural hybrid. G. straminea is the mother of hybrids, but the father is not very clear. In addition, the molecular markers for distinguishing G. robusta from the parental species or closely related species are identified, respectively. Our studies may provide valuable reference for the species identifications of medicinal plants with complex genetic backgrounds.

[Study on Embryonic Development of Four Species of Gentiana (Gentianaceae)].

OBJECTIVE: To study the embryonic development of Gentiana straminea, G. robusta, G. crassicaulis and G. tibetica. METHODS: The seed germination rates, length and width of embryos, starch grains and chloroplasts were observed and analyzed by statistic software. RESULTS: The seed germination rates of the four species were all high. The increase of the length of embryo depended mainly on the increase of the length of hypocotyl. Starch grains were stored in cells and chloroplasts appeared in cotyledons. The process of germination was divided into eight periods. CONCLUSION: The embryo growth characteristics of the four species are recognized, and the results can be used to study the in situ conservation, genetic breeding and cultivation of Sect. Cruciata.

Integration of Lipidomics and Transcriptomics Identifies the Regulation of Lipid Homeostasis as Potential Mechanisms of Konjac Glucomannan against Hepatic Steatosis.

Hepatic steatosis is characterized by substantial disruption in the liver's lipid level regulation. Konjac glucomannan (KGM) is acknowledged as a nutritious food that has the potential to prevent hyperlipidemia. This study utilized lipidomics and transcriptomics to investigate the efficacy of KGM in alleviating high-fat diet-induced hepatic steatosis by regulating lipid homeostasis. The findings indicated that supplementation of KGM for a duration of 10 weeks led to significant decreases in body weight, liver weight, and epididymal fat tissue weight. Furthermore, improvements in lipid concentrations in plasma and liver samples were observed, along with enhancements in glucose tolerance and the mitigation of liver damage. Additionally, lipidomics analysis revealed that the primary differential lipid metabolites were mainly associated with fatty acid metabolism pathways. Transcriptomic analysis showed that KGM significantly altered the gene expression of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the liver. Moreover, KGM demonstrated a significant regulatory impact on the hepatic expression of PPARγ, potentially mitigating hepatic steatosis through modulation of the PPARγ-mediated lipid metabolism pathway. In conclusion, these findings suggest that KGM effectively mitigates steatosis by modulating hepatic lipid metabolites and controlling PPARγ-mediated genes in the liver.

Ganlu formula ethyl acetate extract (GLEE) blocked the development of experimental arthritis by inhibiting NLRP3 activation and reducing M1 type macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored. AIM OF THE STUDY: This study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA. MATERIALS AND METHODS: Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to analyze and identify the chemical constituents within GLEE. Discovery Studio molecular virtual docking technology was utilized to dock the interaction of GLEE with inflammation-related pathway proteins. The GLEE gene library was obtained by transcriptome sequencing. Collagen-induced arthritic（CIA) rats were utilized to assess the antiarthritic efficacy of GLEE. Micro-CT imaging was employed to visualize the rat paw, and ultrasound imaging revealed knee joint effusion. Evaluation of synovial tissue pathological changes was conducted through hematoxylin-eosin staining and saffranine solid green staining, while immunohistochemical staining was employed to assess NLRP3 expression along with inflammatory markers. Immunofluorescence staining was utilized to identify M1 macrophages. RESULTS: Metabolomic analysis via UPLC-Q-TOF-MS identified 28 potentially bioactive compounds in GLEE, which interacted with the active sites of key proteins such as NLRP3, NF-κB, and STAT3 through hydrogen bonds, C-H bonds, and electrostatic attractions. In vitro analyses demonstrated that GLEE significantly attenuated NLRP3 inflammasome activation and inhibited the polarization of bone marrow-derived macrophages (BMDMs) towards the M1 phenotype. In vivo, GLEE not only prevented bone mineral density (BMD) loss but also reduced ankle swelling in CIA rats. Furthermore, it decreased the expression of the NLRP3 inflammasome and curtailed the release of inflammatory mediators within the knee joint. CONCLUSION: GLEE effectively mitigated inflammatory responses in both blood and knee synovial membranes of CIA rats, potentially through the down-regulation of the NLRP3/Caspase-1/IL-1ß signaling pathway and reduction in M1 macrophage polarization.

Comparing massa medicata fermentata before and after charred in terms of digestive promoting effect via metabolomics and microbiome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Massa Medicata Fermentata, a fermented Chinese medicine, is produced by the fermentation of six traditional Chinese medicines. Liu Shenqu (LSQ) and charred Liu Shenqu (CLSQ) have been used for strengthening the spleen and enhancing digestion for over a thousand years, and CLSQ is commonly used in clinical practice. However, it is unclear whether there is a difference in the spleen strengthening and digestion effects between LSQ and CLSQ, as well as their mechanisms of action. AIM OF STUDY: This study aims to compare the effects of LSQ and CLSQ on the digestive function of functional dyspepsia (FD) rats and reveal their mechanisms of action. MATERIALS AND METHODS: SPF grade SD rats were randomly divided into 6 groups: control group, model group, Liu Shenqu decoction low-dosage (LSQ LD) group, Liu Shenqu decoction high-dosage (LSQ HD) group, charred Liu Shenqu decoction low-dosage (CLSQ LD) group, and charred Liu Shenqu decoction high-dosage (CLSQ HD) group. Rats were injected intraperitoneally with reserpine to create an FD model and then treated by intragastric administration. During this period, record the weight and food intake of the animals. After 18 days of treatment, specimens of the gastric antrum, spleen, and duodenum of rats were taken for pathological staining and immunohistochemical detection of Ghrelin protein expression. Enzyme linked immunosorbent assay (ELISA) was used to determine the concentration of relevant gastrointestinal hormones in serum. The 16 S rDNA sequencing method was used to evaluate the effect of cecal contents on the structure of the gut microbiota in experimental rats. Plasma metabolomics analysis was performed using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) to further reveal their mechanism of action. RESULTS: LSQ and CLSQ improved the pathological tissue histological structure of FD rats and increased the levels of MTL and GAS hormones in serum and the levels of ghrelin in the gastric antrum, spleen, and duodenum, while reducing VIP, CCK, and SP hormone levels. The above results showed that the therapeutic efficacy of CLSQ is better than that of LSQ. Futhermore, the mechanism of action of LSQ and CLSQ were revealed. The 16 S rDNA sequencing results showed that both LSQ and CLSQ can improve the composition and diversity of the gut microbiota. And metabolomic analysis demonstrated that 20 metabolites changed after LSQ treatment, and 16 metabolites underwent continuous changes after CLSQ treatment. Further analysis revealed that LSQ mainly intervened in the metabolic pathways of glycerol phospholipid metabolism and arginine and proline metabolism, but CLSQ mainly intervened in the metabolic pathways of ether lipid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. CONCLUSIONS: Both LSQ and CLSQ can improve functional dyspepsia in FD rats, but CLSQ has a stronger improvement effect on FD. Although their mechanisms of action are all related to regulating gastrointestinal hormone secretion, significantly improving intestinal microbiota disorders, and improving multiple metabolic pathways, but the specific gut microbiota and metabolic pathways they regulate are different.

Epidemiological Survey of Congenital Heart Disease Among Children Aged from 2 to 18 in Suo County, Nagqu, Tibet.

Lin, Tian, Huaping Jia, Yunming Li, Yongxing Xu, Bei Zhao, Dong Zheng, Hongfeng Yan, Meihui Zhao, Yanlei Li, Liping Xia, Fengxia Zhou, Cuiping Liu, Ke Ma, Ma Mi, and Jianwen Gu. Epidemiological survey of congenital heart disease among children aged from 2 to 18 in Suo County, Nagqu, Tibet. High Alt Med Biol. 00:000-000, 2024. Background: Studies have reported the prevalence of congenital heart disease (CHD) in parts of Tibet, but relative epidemiological surveys are rare. We aimed to explore the prevalence of CHD in children and its relationship with family history in Suo County, Nagqu, Tibet, an altitude of 3,980 meters. Methods: We recruited 4,002 children aged 2-18 years. Subjects underwent a family history investigation, cardiac auscultation, and clinical manifestation examination and then received echocardiographic screening. Results: The prevalence of CHD among children in Suo County was 0.97% (39 cases), much higher than the prevalence at sea level. The most common subtype was atrial septal defect, accounting for 53.9% of CHD, followed by patent ductus arteriosus (33.3%) and ventricular septal defect (12.8%). We also found that children whose mothers had previously borne children with CHD had a higher risk of CHD than those without (p = 0.002); other factors related to CHD during pregnancy, such as smoking, drinking, drug use, and viral infection, showed no statistical differences between children with and without CHD. Conclusions: The prevalence of CHD in children in Suo County is much higher than at low altitude, consisting mostly of simple forms with left-to-right shunt, with rare complex CHD. These results support implementing diagnostic and treatment plans to prevent CHD in Suo County.

[Identification of medicinal plants used as Tibetan traditional medicine Chuan-Bu based on nrDNA markers].

OBJECTIVE: To identify the common Tibetan herb Chuan-Bu. METHOD: Local herbalists were visited to observe which plants were being used as Chuan-Bu. Samples of the indigenous plants were collected at the same time. Leaf materials were collected from field surveys. Total genomic DNA was extracted from silica gel-dried leaf samples. The PCR products were purified and directly sequenced. RESULT: As the origin of Chuan-Bu in Tibet autonomous region was authenticated, two species were determined, i. e. Euphorbia stracheyiand E. wallichii. Also, based on our earlier research, the origin of Chuan-Bu in Gansu province, is from E. kansuensis. The sequences of ITS1 for E. stracheyi and E. wallichii were 261 bp in size, and 221 bp in ITS2, respectively. The size of the 5.8S coding region was 164 bp for all species examined in the genus. Especially, there was a heterozygous locus in ITS1 (C/G; position 72) for E. stracheyi. The nucleotide divergence between sequences of the 6 species in pairwise comparisons was calculated and the result showed that the variable site could be detected in each pairwise comparison of sequences. Also, there were 8 point mutations in the 5.8S coding region. CONCLUSION: nrDNA ITS sequences can be used as the molecular markers to identify the Tibetan herb Chuan-Bu and such Traditional Chinese Medicines from the same genus Euphorbia as E. lathyris, E. humifusa and E. pekinensis.

Investigation of the chemical profile and anti-inflammatory mechanisms of flavonoids from Artemisia vestita Wall. ex Besser via targeted metabolomics, zebrafish model, and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia vestita Wall. ex Besser is wildly distributed in the western high-altitude area of China and has been used as a Tibetan medicine to treat inflammatory diseases. We previously demonstrated the total flavonoids of Artemisia vestita Wall. ex Besser (TFA) showed obvious anti-inflammatory effects and its content was 276.62 mg/g. However, the chemical profile, active ingredients, and anti-inflammatory mechanisms of TFA are not clear. AIM OF THE STUDY: This study aimed to study the components of TFA, evaluate the anti-inflammatory effects of TFA, and preliminarily predict the anti-inflammatory mechanism of TFA. MATERIALS AND METHODS: TFA was prepared by the semi-biomimetic extraction method and purified by macroporous resin. The components of TFA were analyzed based on LC-MS combined with the targeted metabolomics method. The anti-inflammatory activity of TFA was evaluated using CuSO4-induced and tail cutting-induced zebrafish inflammation models. Based on the network pharmacology method, the anti-inflammatory mechanism of the main components of TFA was preliminarily predicted. RESULTS: A total of 185 components were identified in TFA. TFA showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. According to network pharmacology prediction and experimental verification, 10 compounds were identified as the main active ingredients, including 3,7-di-O-methylquercetin, Hesperetin 5-O-glucoside, Myricitrin, et al. Twenty key targets were recognized, such as TNF, AKT1, VEGFA, MMP9, EGFR, PTGS2 et al. Moreover, the TNF signaling pathway and NOD-like receptor signaling pathway were identified to play vital roles in the anti-inflammatory effects of TFA. CONCLUSIONS: This study revealed the chemical profile of TFA and identified the main active ingredients, key targets, and pathways of TFA in anti-inflammatory effects, which is helpful to elucidate the pharmacodynamic substances and action mechanisms of Artemisia vestita Wall. ex Besser, to promote its clinical rational application.

Isoalantolactone protects against ethanol-induced gastric ulcer via alleviating inflammation through regulation of PI3K-Akt signaling pathway and Th17 cell differentiation.

Gastric ulcer (GU) is one of the most prevalent digestive system diseases in humans, and it has been linked to inflammation. Previous studies have demonstrated the anti-inflammatory potential of isoalantolactone (IAL), a sesquiterpene lactone isolated from Radix Inulae. However, the pharmacological effects of IAL on GU and its mechanism of action are still unclear. Hence, the present study is aimed to investigate the anti-inflammatory potential of IAL on GU. Firstly, we assessed the effect of IAL on ethanol-induced injury of human gastric epithelial cells and the levels of inflammatory cytokines in cell culture supernatants. Then, the anti-inflammatory effects of IAL were confirmed in vivo using zebrafish inflammation models. Furthermore, the mechanism of IAL against GU was preliminarily discussed through network pharmacology and molecular docking studies. Quantitative real-time PCR assays were also used to confirm the mechanism of IAL action. ALB, EGFR, SRC, HSP90AA1, and CASP3 were found for the first time as the key targets of the IAL anti-GU. PI3K-Akt signaling pathway and Th17 cell differentiation were identified to play a crucial role in the anti-GU effects of IAL. In conclusion, we found that IAL has anti-inflammatory effects both in vitro and in vivo, and showed potential protective effects against ethanol-induced GU.

Aspiration thrombectomy versus stent retriever thrombectomy as a first-line approach for cardiogenic cerebral embolism and cryptogenic stroke in large vessels of the anterior circulation.

Subject: This study aims to compare the clinical efficacy of aspiration thrombectomy and stent retriever thrombectomy as first-line approaches for anterior circulation large vessel cardiogenic cerebral embolism and cryptogenic stroke. Method: This retrospective observational study included patients with anterior circulation large vessel cardiogenic cerebral embolism and cryptogenic stroke treated with endovascular therapy. Patients were grouped according to the first-line approach they received: aspiration thrombectomy or stent retriever thrombectomy. The primary outcome measure was the change in the National Institute of Health Stroke Scale (NIHSS) score from preoperative to immediate postoperative and from preoperative to discharge. Secondary indicators included the rate of favorable prognosis at discharge [Modified Rankin Scale (mRS) score ≤ 2], successful vessel recanalization rate [modified Treatment in Cerebral Ischemia (mTICI) score ≥ 2b], time from successful femoral artery puncture to successful vessel recanalization, and perioperative complications. Result: The study included 127 cases, with 1 case withdrawal after enrollment due to a stroke of another determined cause, with 83 in the aspiration thrombectomy group and 43 cases in the stent retriever thrombectomy group. The change in NIHSS score from preoperative to immediate postoperative was 5 (1, 8) in the aspiration thrombectomy group and 1 (0, 4.5) in the stent retriever thrombectomy group. The change from preoperative to discharge was 8 (5, 12) in the aspiration thrombectomy group and 4 (0, 9) in the stent retriever thrombectomy group. The aspiration thrombectomy group exhibited significantly better prognosis rates and shorter time from successful femoral artery puncture to successful vessel recanalization. There were no significant differences between the two groups in terms of successful vessel recanalization rates and perioperative complications. Conclusion: As a first-line approach for anterior circulation large vessel cardiogenic cerebral embolism and cryptogenic stroke, aspiration thrombectomy leads to better improvement in neurological functional deficits and prognosis rates compared to stent retriever thrombectomy.

A novel clinical prediction scoring system of high-altitude pulmonary hypertension.

Background: High-altitude pulmonary hypertension (HAPH) is a common disease in regions of high altitude where performing right heart catheterization (RHC) is challenging. The development of a diagnostic scoring system is crucial for effective disease screening. Methods: A total of 148 individuals were included in a retrospective analysis, and an additional 42 residents were prospectively enrolled. We conducted a multivariable analysis to identify independent predictors of HAPH. Subsequently, we devised a prediction score based on the retrospective training set to anticipate the occurrence and severity of HAPH. This scoring system was further subjected to validation in the prospective cohort, in which all participants underwent RHC. Results: This scoring system, referred to as the GENTH score model (Glycated hemoglobin [OR = 4.5], Echocardiography sign [OR = 9.1], New York Heart Association-functional class [OR = 12.5], Total bilirubin [OR = 3.3], and Hematocrit [OR = 3.6]), incorporated five independent risk factors and demonstrated strong predictive accuracy. In the training set, the area under the curve (AUC) values for predicting the occurrence and severity of HAPH were 0.851 and 0.832, respectively, while in the validation set, they were 0.841 and 0.893. In the validation set, GENTH score model cutoff values of ≤18 or >18 points were established for excluding or confirming HAPH, and a threshold of >30 points indicated severe HAPH. Conclusions: The GENTH score model, combining laboratory and echocardiography indicators, represents an effective tool for distinguishing potential HAPH patients and identifying those with severe HAPH. This scoring system improves the clinical screening of HAPH diseases and offers valuable insights into disease diagnosis and management.

A phytoexclusion strategy for reducing contamination risk of rice based on low-Cd natural variations pyramid of root transporters.

Cadmium pollution in rice is a threat to human health. Phytoexclusion is an effective strategy to reduce the Cd accumulation. Soil-to-root is the first step of Cd entering rice and plays a crucial role in Cd accumulation, so targeting root transporters could be an effective approach for phytoexclusion. This study utilized single-gene & multi-gene joint haplotype analysis to reveal the law of natural variations. The result showed that natural variations of rice root transporters assembled regularly following a certain pattern, rather than randomly. A total of 3 dominant nature variation combinations with 2 high-Cd combinations and 1 low-Cd combination were identified. In addition, indica-japonica differentiation was observed, with indica germplasms harboring high-Cd combinations while japonica germplasms harboring. In Chinese rice landraces, most of the collected indica landraces contained high-Cd combinations, indicating a high Cd contamination risk in indica landraces in terms of both phenotype and genotype. To address this issue, multiple superior low-Cd natural variations were pyramided to create two new low-Cd germplasms. In both pond and farmland trials, the ameliorated rice grain Cd did not exceed safety standards. This research provided a framework for future phytoexclusion, thus to reduce Cd-contamination risk in soil-rice system.

Collagen scaffolds tethered with bFGF promote corpus spongiosum regeneration in a beagle model.

Regeneration of the corpus spongiosum helps prevent complications following urethral reconstruction, but currently there is a lack of effective therapeutic methods in clinic. In previous studies, we fabricated a fusion protein collagen-binding domain (CBD)-basic fibroblast growth factor (bFGF) that specifically binds to and releases from collagen biomaterials. We demonstrated that CBD-bFGF could promote angiogenesis and tissue regeneration in vivo. In this study, we established a beagle model with extensive urethral defects, and reconstructed the defects with collagen biomaterials that were unmodified or modified with CBD-bFGF. The results demonstrate that CBD-bFGF promotes corpus spongiosum regeneration resulting in improved outcomes following urethral reconstruction. Modifying collagen biomaterials with CBD-bFGF may represent an effective strategy for urethral substitution in urethral reconstruction.

Comparative efficacy and acceptability of endothelin receptor antagonists for pulmonary arterial hypertension: A network meta-analysis.

BACKGROUND: Endothelin receptor antagonists (ERAs) such as ambrisentan, sitaxsentan, bosentan and macitentan are primary drug therapies for pulmonary arterial hypertension (PAH) patients. However, the optimal drugs for PAH remained controversial due to heterogeneous nature of randomized control trials (RCTs). METHODS: Apart from traditional meta-analysis, network meta-analysis (NMA) was performed in this study for multiple comparisons among PAH therapies. The 6 minute walking distance (6MWD) and clinical worsening were efficacy outcomes whereas serious adverse effects (SAE) and all-cause discontinuation were acceptability outcomes. The weighted mean difference (WMD) and odds ratio (OR) along with their 95% confidence interval (95% CI) or 95% credible interval (95% CrI) were used to evaluate the positive and negative effects of these therapies on PAH patients. RESULTS: By synthesizing direct evidence from 10 studies with a total number of 2172 patients, we discovered that all of the four PAH therapies significantly increased the average 6MWD in comparison to the placebo (P-value<0.05). Moreover, bosentan and ambrisentan both showed significant association with a decrease in the risk of clinical worsening compared to placebo. Regarding of all-cause discontinuation, ambrisentan is the only therapy which was significantly associated with a risk decrease compared to placebo. However, there was no sufficient evidence suggesting significant difference in any efficacy or acceptability outcomes between any two of the PAH therapies (P-value>0.05). CONCLUSION: Ambrisentan could be considered as the most appropriate therapy among the four ERAs for PAH patients. Bosentan also behaved well, but it is not as safe as ambrisentan.