LncRNA MTC-p65 Protein Mediates Skin Fibroblast Proliferation in Liaoning Cashmere Goat by Regulating the Nuclear Factor-Kappa B Signaling Pathway.

The aim of this study is to investigate the activation of NF-κB signaling pathway and the regulation of the expression of genes related to chorionic villus growth by the binding of LncRNA MTC (XLOC_005914) and p65 (transcription factor p65 [Capra hircus], XP_017898873.1). In addition, the regulation of LncRNA MTC and p65 binding on the proliferation of Liaoning Cashmere Goat skin fibroblasts is investigated. The upregulation of LncRNA MTC promoted the proliferation of skin fibroblasts, and the NF-κB signaling pathway played an important role in this process. Compared with the negative control (NC group), the expression of TNFα and NFKB2(NF-κB) genes was highly significantly up-regulated (P < 0.001), and NFKBIA(IκBɑ) genes were highly significantly down-regulated (P < 0.01) after LncRNA MTC overexpression (OE group). The expression levels of TNFα and NFκB-P-p65 proteins were upregulated in the OE group; NF-κB-p65 expression levels were upregulated in the nucleus, IκBα expression levels were downregulated in the cytoplasm, and P-IκBα expression levels were upregulated. LncRNA MTC and p65 proteins were co-localized in the cells. Meanwhile, LncRNA MTC and p65 protein showed significant nucleation in the OE group. RNA pull-down and LC-MS/MS verified that p65 protein was indeed an interacting protein of LncRNA MTC. LncRNA MTC binds to p65 protein, upregulates the expression of TNFα protein, nucleates p65 protein, and activates NF-κB signaling pathway to promote the proliferation of skin fibroblasts in Liaoning Cashmere Goat.

Cultural Dimensions Moderate the Association between Loneliness and Mental Health during Adolescence and Younger Adulthood: A Systematic Review and Meta-Analysis.

Cultural factors, such as country or continent, influence the relationship between loneliness and mental health. However, less is known about how cultural dimensions moderate this relationship during adolescence and younger adulthood, even if these dimensions manifest as country or continent differences. This study aims to examine the potential influence of Hofstede's cultural dimensions on this relationship using a three-level meta-analysis approach. A total of 292 studies with 291,946 participants aged 10 to 24 were included in this study. The results indicate that cultural dimensions, such as individualism vs. collectivism, indulgence vs. restraint, power distance, and long-term vs. short-term orientation, moderated the associations between loneliness and social anxiety, stress, Internet overuse, and negative affect. The association between loneliness and mental health was not moderated by cultural dimensions, such as masculinity and uncertainty avoidance. These findings suggest that culture's influence on the association between loneliness and mental health is based on a domain-specific mechanism.

CD163 as a Potential Biomarker-associated Immune Inflammation in Diabetes Mellitus: A Systematic Review and Bioinformatics Analysis.

BACKGROUND: Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific mechanism. OBJECTIVES: In this study, we aimed to investigate CD163 as a potential biomarker associated with immune inflammation in diabetes mellitus through a systematic review and bioinformatics analysis. METHODS: We searched PubMed, Web of Science, the Cochrane Library, and Embase databases with a time limit of September 2, 2022. Furthermore, we conducted a systematic search and review based on PRISMA guidelines. Additionally, diabetic gene expression microarray datasets GSE29221, GSE30528, GSE30529, and GSE20966 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) for bioinformatics analysis. The PROSPERO number for this study is CRD420222347160. RESULTS: Following the inclusion and exclusion criteria, seven articles included 1607 patients, comprising 912 diabetic patients and 695 non-diabetic patients. This systematic review found significantly higher levels of CD163 in diabetic patients compared to non-diabetic patients. People with diabetes had higher levels of CRP expression compared to the control group. Similarly, two of the three papers that used TNF- α as an outcome indicator showed higher expression levels in diabetic patients. Furthermore, IL-6 expression levels were higher in diabetic patients than in the control group. A total of 62 samples were analyzed by bioinformatics (33 case controls and 29 experimental groups), and 85 differential genes were identified containing CD163. According to the immune cell correlation analysis, CD163 was associated with macrophage M2, γδ T lymphocytes, macrophage M1, and other immune cells. Furthermore, to evaluate the diagnostic performance of CD163, we validated it using the GSE20966 dataset. In the validation set, CD163 showed high diagnostic accuracy. CONCLUSION: This study suggests CD163 participates in the inflammatory immune response associated with diabetes mellitus and its complications by involving several immune cells. Furthermore, the results suggest CD163 may be a potential biomarker reflecting immune inflammation in diabetic mellitus.

Production mechanism of high-quality carbon black from high-temperature pyrolysis of waste tire.

High-temperature pyrolysis of waste tires is a promising method to produce high-quality carbon black. In this study, carbon black formation characteristics were investigated during tire pyrolysis at 1000-1300 °C with residence times of < 1 s, 1-2 s, and 2-4 s. It is shown that with temperature increasing from 1000 °C to 1300 °C carbon black yield was increased from 10% to 27% with residence times of 2-4 s. Carbon black exhibited a core-shell nanostructure over 1100 °C and the graphitization degree was promoted with the temperature and residence time. While the mean particle diameter decreased with the temperature to 69 nm at 1300 °C and further increased by residence time. The molecular-level evolution from tire to initial carbon black was further revealed by reactive force field molecular dynamics simulations. Light oil, gas, and radicals were transformed to initial cyclic molecules and long carbon chains via carbon-addition-hydrogen-migration, H-abstraction-C2H2-addition, and radical-chain reactions, subsequently forming PAHs. The coupling of PAHs aliphatic side chains formed large graphene layers that gradually bent to fullerene-like cores and generated incipient carbon black. The process mechanism from volatiles evolution to carbon black was proposed, which may be helpful for obtaining high-quality carbon black from high-temperature pyrolysis of waste tires.

Effects of lncRNA MTC on protein expression in skin fibroblasts of Liaoning Cashmere goat based on iTRAQ technique.

Existing experiments have found a new intergenic lncRNA activated by melatonin, which is called lncRNA MTC. However, the regulatory mechanism of lncRNA MTC in Liaoning Cashmere goat skin fibroblasts has not been clarified. Specific knockdown of lncRNA MTC inhibits cell proliferation and increases apoptosis. iTRAQ reagent was used for relative and absolute quantification of proteins in lncRNA MTC-KD and NC groups to evaluate changes in protein expression during dermal fibroblast development following lncRNA MTC deletion. A total of 5931 proteins were found in Liaoning Cashmere goat skin fibroblasts, of which 123 were differentially expressed, including 32 up-regulated proteins and 91 down-regulated proteins. Of the 91 down-regulated proteins, 32 act mainly through related pathways (e.g., cell cycle, mitochondrial function, ribosomal structure, vesicular transport, cytoskeletal components and skin morphogenesis). LncRNA MTC facilitates the proliferation of Liaoning Cashmere goat skin fibroblasts by regulating ITGB5, TlN2, CTSS, POLG, RAP1B, CHAF1A, CDCA8 and other proteins involved in cell proliferation. The results of this study provide some candidate proteins for the in-depth investigation of the molecular mechanism of lncRNA MTC, which facilitates hair growth in cashmere goats and provides more insights into their regulatory networks and biochemical pathways.

Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

[Effects of astragaloside IV on delaying kidney aging and its mechanisms].

OBJECTIVE: To investigate the mechanisms of Astragaloside Ⅳ on inhibiting apoptosis and delaying kidney aging in rats by regulating SIRT1/p53 signaling pathway. METHODS: The aging model was established by subcutaneous injection of D-galactose 200 mg/(kg·d). SPF-grade healthy male SD rats were randomly divided into 4 groups: normal control group (intragastric infusion of 5 ml/(kg·d) normal saline), aging model group (intragastric infusion of 5 ml/(kg·d) normal saline), Astragaloside IV group (intragastric infusion of 40 mg/(kg·d) Astragaloside IV),and SRT1720 group( intragastric infusion of 20 mg/(kg·d) SRT1720), with 10 rats in each group. After 8 weeks, the serum samples of rats were collected to detect the levels of renal function (creatinine and urea nitrogen) and senescent associated secretory phenotype (TGF-ß and IL-6) by ELISA. The renal tissues of rats were obtained for HE and Masson staining. The protein and mRNA expressions of SIRT1, p53, Bcl-2, Bax, p21 and pRb were detected by Western blot and RT-PCR. RESULTS: Serum creatinine and urea nitrogen levels in the aging model group were higher than those in the normal group, but there was no significant difference in each group (P＞0.05). The serum levels of TGF-ß and IL-6 in the aging model group were higher than those in the normal group (P＜0.05), and which in the Astragaloside IV group and SRT1720 group were lower than those in the model group (P＜0.05). There was no significant differences between Astragaloside IV group and SRT1720 group (P＞0.05). The results of pathological staining of renal tissues showed that, compared with the normal group, the renal tubules dilated, local atrophy, infiltration of inflammatory cells and proliferation of collagen fibers were observed in the aging model group. Compared with the aging model group, the pathological changes were alleviated in Astragaloside IV group and SRT1720 group. The results of Western blot and RT-PCR showed that, compared with the normal group, the protein and mRNA expressions of SIRT1 and pRb in the renal tissue of the aging group were decreased, the protein expression of Bcl-2 was decreased(P＜0.05), and the protein and mRNA expressions of p53 and p21 were increased, the protein expression of Bax was increased(P＜0.05). Compared with the aging group, Astragaloside IV and SRT1720 improved the above-mentioned indexes (P＜0.05). CONCLUSION: Astragaloside IV can delay kidney aging by regulating the SIRT1/p53 signaling pathway.

Study on the roles of melatonin in regulating dermal fibroblast growth in Liaoning cashmere goats by transcriptome sequencing.

In this study, the genes related to the Downy growth of Liaoning cashmere goats were screened for their expression with simultaneous melatonin administration, so as to investigate the effects of target genes on the proliferation of skin fibroblasts in this animal species. Genes related to the villus growth of skin fibroblasts were screened by in vitro transcriptome sequencing and verified by qPCR. In addition, gene overexpression and interference were used to study the effects of target genes on the proliferation of skin fibroblasts. Groups treated with M1_24H, M2_24H and M2_72H exhibited significant differences compared with the control group. Among them, the differentially expressed transcripts in the M2_72H group were significantly enriched in the TNF and NOD-like receptor signaling pathways, which are associated with the villus. In addition, eight differentially expressed genes were screened from the TNF and the NOD-like receptor signaling pathways. Verification by qPCR showed that the expression of TNF-α, IL-6, TNFAIP3, PYCARD and NFKBIA genes were significantly upregulated, which was consistent with the sequencing results. Melatonin treatments can significantly lead to an increase in the expression of IL-6 and TNF-α genes. Besides, melatonin treatments can affect cashmere growth in Liaoning cashmere goats by regulating several signaling pathways, including TNF, NOD-like receptor and NF-κB.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Bazi Bushen Capsules on Anti-aging： A Review / 中国实验方剂学杂志

The decline of body function and senile diseases caused by aging seriously affect human health and life span， which is an important topic in the field of life science. Bazi Bushen capsules is a representative Chinese patent medicine for tonifying essence， invigorating Qi and anti-aging， guided by Qiluo doctrine， and essence， Qi and spirit theory. Previous pharmacological and clinical studies have confirmed that this preparation has the comprehensive advantages of anti-aging， and prevention and treatment of aging-related diseases. Among them， pharmacological studies showed that Bazi Bushen capsules had the effect of improving the appearance status of mice， improving the level of sex hormones， inhibiting the formation of atherosclerosis， improving cardiac function， improving learning and memory cognitive ability， improving neurological function， improving osteoporosis and muscle function， improving sperm count and quality. The mechanism was related to the up-regulation of the recombinant sirtuin （SIRT6） level， down-regulation of the levels of aging-related proteins p53 and p16， up-regulation of telomerase reverse transcriptase level， and alleviation of inflammation and oxidative response. Clinical studies have proved that it can improve the symptoms of patients with kidney essence deficiency， improve exercise ability， and improve the sexual function of impotence patients. Anti-aging research of Bazi Bushen capsules based on Qiluo doctrine fully embodies the new mode of academic innovation and transformation of traditional Chinese medicine （TCM） with the combination of "theory-new drug-experiment-clinic"， which has made a demonstration for the anti-aging research of TCM.

Factors contributing to spatial-temporal variations of observed oxygen concentration over the Qinghai-Tibetan Plateau.

Oxygen (O2) is the most abundant molecule in the atmosphere after nitrogen. Previous studies have documented that oxygen concentration remains nearly constant (20.946%) at all altitudes. Here we show for the first time that oxygen concentration varies significantly from earlier consensus and shows strong spatial and seasonal differences. Field observations on the Qinghai-Tibetan Plateau (QTP) indicate oxygen concentration of 19.94-20.66% (2018, n = 80), 19.98-20.78% (2019, n = 166) and 19.97-20.73% (2020, n = 176), all statistically different from earlier reports (p < 0.001) and are lower than the nearly constant. The mean oxygen concentration in summer (20.47%) is 0.31% higher than that of winter (20.16%) (n = 53) at identical locations in 2019, sampled in the Qilian Mountains, northwest QTP. We used LMG (The Lindeman, Merenda and Gold) method to estimate the relative contributions of altitude, air temperature and vegetation index (Fractional Vegetation Cover, FVC and Leaf Area Index, LAI) to oxygen concentration, which are 47%, 32% and 3% (FVC, R2 = 82%); 45%, 30% and 7% (LAI, R2 = 82%), respectively. These findings provide a new perspective for in-depth understanding on population risk in high altitude regions in the context of global climate change, to ensure the health and safety of residents and tourists in high altitude regions and promoting the stability, prosperity and sustainable development of high-altitude regions worldwide.

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

Rice drought risk assessment under climate change: Based on physical vulnerability a quantitative assessment method.

Drought is the most serious natural disaster causing severe damage to agriculture. Drought impacts on rice (Oryza sativa) production present a major threat to future global food security. In this paper, the Environmental Policy Integrated Climate (EPIC) model was used to simulate the growth of rice, in different periods (short-term (2019-2039), medium-term (2040-2069), long-term (2070-2099)), based on multiple Representative Concentration Pathways (RCP) scenarios. Drought intensity and rice physical vulnerability curves were assessed, based on the output parameters of EPIC, to evaluate global rice yield risk, due to drought. The results show that the average expected loss rate of global rice yield may reach 13.1% (±0.4%) in the future. The high-risk area of rice drought is mainly located in the north of 30°N. The fluctuation of rice drought risk and the proportion of increased risk areas will increase significantly. About 77.6% of the changes in rice drought risk are explained by variations in shortwave radiation (r = 0.88). Projections show that the average value of daily shortwave radiation increases by 1 W/m2 during the rice growth period, accompanied by an expected rice yield loss rate of about 12.7%. The rice drought risk methods presented in this paper provide plausible estimates of forecasting future drought risk under climate change, and address challenges of sparse data; we believe these methods can be applied to decisions for reducing drought-related crop losses and ensuring global food security.

Salsalate reverses metabolic disorders in a mouse model of non-alcoholic fatty liver disease through AMPK activation and caspase-6 activity inhibition.

Salsalate, an ester formed by 2 salicylic acid molecules, has beneficial effect against metabolic disorders in clinical trials and in animal studies. This study focused on the mechanistic aspects of salsalate activity against non-alcoholic fatty liver disease (NAFLD). Using high-fat diet (HFD) fed mice, we showed that salsalate treatment decreased body-weight gains, reduced white adipose tissue mass and improved glycaemic control. Mice in salsalate-treated group also had reduced obese adipose tissue and hepatic macrophage infiltration and inflammation and adipogenesis gene expression. Histology analysis revealed predominant decreases in hepatosteatosis, including both macrovesicular and microvesicular steatoses. The treatment reversed AMPK activity repression that was accompanied by reduced caspase-6 activity and cleavage. Enzymatic assay and cell culture studies showed that salsalate promoted AMPK activation by directly activating AMPK. This study links salsalate effect against metabolic disorders to its activity on reversion of AMPK repression in NAFLD mice and on suppression of adipogenic gene induction.

Design, synthesis and biological evaluation of pyrazolo3,4-

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Predictive value of soluble urokinase-type plasminogen activator receptor combined with alpha-fetoprotein and model for end-stage liver disease score in short-term prognosis assessment of patients with chronic hepatitis B related acute-on-chronic liver failure / 中华传染病杂志

Objective:To investigate the predictive value of serum soluble urokinase-type plasminogen activator receptor (suPAR) combined with alpha-fetoprotein (AFP) and model for end-stage liver disease (MELD) score in short-term prognosis assessment of patients with chronic hepatitis B (CHB) related acute-on-chronic liver failure (ACLF).Methods:From January 2018 to May 2020, 66 patients with CHB related ACLF from Fuzhou First People′s Hospital were enrolled. After 90 days of follow-up, the patients with CHB related ACLF were divided into death group and survival group according to the outcome. Meanwhile, 30 patients with CHB were enrolled by simple random sampling method. The differences of serum suPAR in patients with CHB related ACLF and patients with CHB were analyzed. The values of suPAR, AFP and MELD score were compared between death group and survival group in patients with CHB related ACLF. The predictive value of suPAR, AFP, MELD score, Child-Turcotte Pugh score (CTP score) and suPAR combined with AFP and MELD score in the short-term prognosis of patients with CHB related ACLF were analyzed by area under the receiver operator characteristic curve (AUROC). Data were analyzed by two independent sample t test or non-parametric test. Results:The serum suPAR level of patients with CHB related ACLF was (9.6±0.8) ln ng/L, which was higher than that of patients with CHB ((8.0±0.3) ln ng/L). The difference was statistically significant ( t=14.533, P<0.01). The suPAR and MELD score of patients with CHB related ACLF in the death group were (9.9±0.7) ln ng/L and 29.6 (7.1) points, respectively, which were higher than those in the survival group ((9.4±0.7) ln ng/L and 21.0 (5.0) points, respectively). The AFP level in the death group was 45.9 (108.1) μg/L, which was lower than that in the survival group (209.3 (187.1) μg/L). There were significant differences in suPAR ( t=2.895, P=0.005), MELD score ( Z=4.708, P<0.01) and AFP ( Z=3.051, P<0.01) between the death group and the survival group. AUROC of suPAR (0.741, P=0.001), AFP (0.724, P=0.002) and MELD score (0.885, P<0.01) had predictive value for death in patients with CHB related ACLF. The sensitivities of suPAR, AFP, MELD score, CTP score and suPAR combined with AFP and MELD score were 84.6%, 73.1%, 88.5%, 96.2% and 84.6%, respectively, and the specificities were 75.0%, 72.5%, 70.0%, 52.5% and 92.5%, respectively. The AUROC of suPAR combined with AFP and MELD score was 0.871 ( P<0.01), which was higher than that of CTP score (0.793, P<0.01). Conclusions:Serum suPAR is increased in patients with CHB related ACLF. SuPAR combined with AFP and MELD score could apply in the prognostic value for patients with CHB related ACLF.

Can mirror reading reverse the flow of time? Evidence from Japanese speakers.

Accumulating evidence over the last two decades has established the causal role of a unidirectional orthography in shaping speakers' mental representations of time. Casasanto and Bottini (Journal of Experimental Psychology: General, 143, 473-479, 2014) extended previous findings by showing that exposure to mirror-reversed orthography of speakers' native language could completely redirect their mental timelines within minutes. However, the question of whether such a causal effect of writing direction on temporal cognition can be identified in speakers whose native languages adopt bidirectional orthographies remains underexplored in the literature. To address this issue, the present study focused on Japanese which uses bidirectional writing systems, one proceeding horizontally from left to right (HLR) and one vertically from top to bottom (VTB). Two experiments were performed, and the tasks asked participants to process standard/mirror orthography prime questions about time arranged horizontally or vertically, followed by horizontal or vertical arrays of pictorial target stimuli about temporal relations. Results demonstrated that Japanese speakers encoded passage of time into a top-to-bottom linear path commensurate with the VTB writing direction, but they did not align their mental representations of time with the HLR writing orientation. Accordingly, exposure to mirror-reversed bidirectional orthographies redirected Japanese speakers' vertical but not horizontal space-time mappings. Theoretical implications concerning the causal effects of bidirectional orthographies and the generalizability of the representational flexibility of time maintained by Casasanto and Bottini (Journal of Experimental Psychology: General, 143, 473-479) are discussed.