Dose-effect of long-snake-like moxibustion for chronic fatigue syndrome: a randomized controlled trial.

BACKGROUND: The dose-effect relationship of Long-snake-like moxibustion for chronic fatigue syndrome (CFS) remains poorly understood. In order to address this gap, we designed this trial to assess the association between different treatment duration of Long-snake-like moxibustion and its effects on CFS based on the combination measurements of the subjective patient-reported scales with objective medical infrared imaging technology─Thermal Texture Maps (TTM). METHODS: From December 2020 to January 2022, 60 female CFS patients were recruited and equally allocated to two groups: Group A, receiving 60-min Long-snake-like moxibustion per treatment, and Group B, receiving 30-min Long-snake-like moxibustion per treatment. The treatment was administered 3 times per week for a total of 4 weeks. The primary outcome was defined as the improvement of symptoms measured by the Fatigue scale-14 (FS-14), and secondary outcomes were designated as the improvement in Symptoms Scale of Spleen-Kidney Yang Deficiency, Self-rating depression scale, and Self-rating anxiety scale. TTM scanning was employed twice for CFS patients (before and after 4-week treatment) and once for Healthy control subjects (HCs). RESULTS: At week 4, the scores of FS-14 and Symptoms Scale of Spleen-Kidney Yang Deficiency in Group A were significantly lower than those in Group B (physical fatigue: 5.00 vs. 6.00, with 95%CI - 2.00 to 0.00, p = 0.003; FS-14 total score: 8.00 vs. 9.00, with 95%CI - 3.00 to 0.00, p = 0.012; total score of Symptoms Scale of Spleen-Kidney Yang Deficiency: 9.80 vs. 13.07, with 95%CI - 5.78 to - 0.76, P = 0.012). All thermal radiation values of the two groups increased, and statistical differences in ΔTs between Group A and HCs were not obtained. More significant correlations between symptoms improvements and ΔT changes were observed in Group A, and its ΔT changes in Upper Jiao, Shenque (CV8), Zhongwan (CV12), Danzhong (CV17), Zhiyang (GV9), Dazhui (GV14), upper arm, thoracic segments, lumbar segments, renal region, popliteal fossa strongly correlated with the improvement of Spleen-Kidney Yang Deficiency symptoms. CONCLUSIONS: In the same course of treatment, the positive dose-effect relationship was found between the treatment duration of Long-snake-like moxibustion and CFS effect assessment. 60-min Long-snake-like moxibustion per treatment were associated with optimal clinical response and TTM improvement. TRIAL REGISTRATION: Chinese Clinical Trail Registry (No. ChiCTR2000041000, date of registration: 16 December 2020), http://www.chictr.org.cn/showproj.aspx?proj=62488.

Identification of the potential association between SARS-CoV-2 infection and acute kidney injury based on the shared gene signatures and regulatory network.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is identified as the cause of coronavirus disease 2019 (COVID-19) pandemic. Acute kidney injury (AKI), one of serious complications of COVID-19 infection, is the leading contributor to renal failure, associating with high mortality of the patients. This study aimed to identify the shared gene signatures and construct the gene regulatory network between COVID-19 and AKI, contributing to exploring the potential pathogenesis. METHODS: Utilizing the machine learning approach, the candidate gene signatures were derived from the common differentially expressed genes (DEGs) obtained from COVID-19 and AKI. Subsequently, receiver operating characteristic (ROC), consensus clustering and functional enrichment analyses were performed. Finally, protein-protein interaction (PPI) network, transcription factor (TF)-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory network were systematically undertaken. RESULTS: We successfully identified the shared 6 candidate gene signatures (RRM2, EGF, TMEM252, RARRES1, COL6A3, CUBN) between COVID-19 and AKI. ROC analysis showed that the model constructed by 6 gene signatures had a high predictive efficacy in COVID-19 (AUC = 0.965) and AKI (AUC = 0.962) cohorts, which had the potential to be the shared diagnostic biomarkers for COVID-19 and AKI. Additionally, the comprehensive gene regulatory networks, including PPI, TF-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory networks were displayed utilizing NetworkAnalyst platform. CONCLUSIONS: This study successfully identified the shared gene signatures and constructed the comprehensive gene regulatory network between COVID-19 and AKI, which contributed to predicting patients' prognosis and providing new ideas for developing therapeutic targets for COVID-19 and AKI.

Radiomics model based on shear-wave elastography in the assessment of axillary lymph node status in early-stage breast cancer.

OBJECTIVES: To develop and validate an ultrasound elastography radiomics nomogram for preoperative evaluation of the axillary lymph node (ALN) burden in early-stage breast cancer. METHODS: Data of 303 patients from hospital #1 (training cohort) and 130 cases from hospital #2 (external validation cohort) between Jun 2016 and May 2019 were enrolled. Radiomics features were extracted from shear-wave elastography (SWE) and corresponding B-mode ultrasound (BMUS) images. The minimum redundancy maximum relevance and least absolute shrinkage and selection operator algorithms were used to select ALN status-related features. Proportional odds ordinal logistic regression was performed using the radiomics signature together with clinical data, and an ordinal nomogram was subsequently developed. We evaluated its performance using C-index and calibration. RESULTS: SWE signature, US-reported LN status, and molecular subtype were independent risk factors associated with ALN status. The nomogram based on these variables showed good discrimination in the training (overall C-index: 0.842; 95%CI, 0.773-0.879) and the validation set (overall C-index: 0.822; 95%CI, 0.765-0.838). For discriminating between disease-free axilla (N0) and any axillary metastasis (N + (≥ 1)), it achieved a C-index of 0.845 (95%CI, 0.777-0.914) for the training cohort and 0.817 (95%CI, 0.769-0.865) for the validation cohort. The tool could also discriminate between low (N + (1-2)) and heavy metastatic ALN burden (N + (≥ 3)), with a C-index of 0.827 (95%CI, 0.742-0.913) in the training cohort and 0.810 (95%CI, 0.755-0.864) in the validation cohort. CONCLUSION: The radiomics model shows favourable predictive ability for ALN staging in patients with early-stage breast cancer, which could provide incremental information for decision-making. KEY POINTS: • Radiomics analysis helps radiologists to evaluate the axillary lymph node status of breast cancer with accuracy. • This multicentre retrospective study showed that radiomics nomogram based on shear-wave elastography provides incremental information for risk stratification. • Treatment can be given with more precision based on the model.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus: a retrospective study from 2017 to 2021.

BACKGROUND: Nondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy. METHODS: This is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD. RESULTS: A total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257-8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049-8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251-2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474-6.044; P = 0.002).. CONCLUSIONS: A DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

Risk factors for twin pregnancy in women undergoing double cleavage embryo transfer.

BACKGROUND: Two or more embryo transfers have been used to increase the success rate of live birth in traditional in vitro fertilization (IVF) strategy at the expense of increased risks of multiple pregnancy and adverse perinatal outcomes. The decision regarding the elective single embryo transfer or double embryo transfer remains inconclusive. The aim of this study was to investigate the risk factors for twin pregnancy in IVF. METHODS: Participants who underwent their first fresh IVF cycle where two cleavage stage embryos were transferred in Women's Hospital of Zhejiang University between January 2010 and December 2018 were included in this retrospective cohort study. The primary outcome was twin delivery. Secondary outcomes included preterm birth and low birth weight RESULTS: Fifteen thousand four hundred fifty-nine women were available for final analysis, in which 1511 women resulted in twin delivery and 4788 women had singleton delivery. Female age over 35 was associated with reduced rates of twin pregnancy compared with female age at or less than 35 (9.5% vs 25.1%, aRR = 0.38 (0.27. 0.55)). Poor-type endometrium was associated with reduced rates of twin pregnancy (19.2% vs 27.5%, aRR = 0.75 (0.58. 0.96)). Two good-quality embryos for transfer was associated with significantly higher rates of twin pregnancy compared with one good-quality or none good-quality embryo (26% vs 12.8% vs 9.3%, aRR = 0.56 (0.45. 0.70), aRR = 0.44(0.26. 0.74)). Female age over 35 and none or one good-quality embryo for transfer were associated with reduced rate of low birth weight and preterm birth. CONCLUSION: Women with age over 35, poor-type endometrium, one good-quality embryo or none good-quality embryo were associated with reduced rate for twin pregnancy.

Arsenic exposure during juvenile and puberty significantly affected reproductive system development of female SD rats.

Infertility affects about 10-15% couples over the world, among which a large number of cases the underlying causes are still unclear. Recent studies suggest that environmental factors may play an important role in these idiopathic infertilities. Arsenic is a heavy metal found in drinking water over the world. Its effect on the development of female reproductive system at the environmental-relevant levels is still largely unknown. To test the hypothesis that arsenic exposure during juvenile and puberty may affect sex maturation and female reproductive system development, SD rats of 3 weeks of age were exposed to arsenic with environmental-relevant levels (0, 0.02, 0.2, or 2 mg/L, n = 16/group) through drinking water for about 44 days until the rats reached adulthood (65 days of age). Arsenic exposure significantly reduced the weights of both ovary and uterus without affecting the body weight. Also, arsenic exposure disturbed estrus cycles and reduced the numbers of primordial follicles and corpora lutea while increased atretic follicles. In addition, arsenic reduced serum levels of estradiol, progesterone and testosterone but increased LH and FSH levels in dose-dependent manners. QPCR and Western blot experiments indicated arsenic selectively down-regulated ovarian steroidogenic-related proteins FSHR, STAR, CYP17A1, HSD3B1 and CYP19A1 and signaling molecules PKA-ERK-JNK-cJUN, without affecting AKT and CREB. As about reproductive capacity, arsenic-exposed dams had smaller pups, reduced litter size and lower number of male pups without a change in female pups. In conclusion, juvenile and pubertal arsenic exposures at environmental-relevant levels significantly reduced reproductive functions and capacity by adult. Since the lowest effective dose is very close to the government safety standards, the relevancy of arsenic over exposure to reproductive defects in human deserves further study.

CD100 modulates cytotoxicity of CD8+ T cells in patients with acute myocardial infarction.

BACKGROUND: CD100 is an immune semaphorin family member that highly expressed on T cells, which take part in the development of acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) are important mediators for membrane-bound CD100 (mCD100) shedding from T cells to generate soluble CD100 (sCD100), which has immunoregulatory effect on T cells. The aim of this study was to investigate modulatory role of CD100 on CD8+ T cell activity in AMI patients. METHODS: Peripheral sCD100 and MMP-2 level, as well as mCD100 level on T cells was assessed in patients with stable angina pectoris (SAP), unstable angina pectoris (UAP), and AMI. The regulatory function of MMP-2 on mCD100 shedding, sCD100 formation, and cytotoxicity of CD8+ T cells was analyzed in direct and indirect contact co-culture system. RESULTS: AMI patients had higher peripheral sCD100 and lower mCD100 expression on CD8+ T cells in comparison with SAP, UAP, and controls. CD8+ T cells in AMI patients showed elevated direct cytotoxicity, enhanced cytokine production, and increased perforin/granzyme B secretion. Recombinant sCD100 stimulation promoted cytolytic function of CD8+ T cells in controls and AMI patients. Furthermore, AMI patients also had elevated circulating MMP-2 level. Recombinant MMP-2 stimulation induced mCD100 shedding from CD8+ T cells and sCD100 generation, resulting in enhancement of CD8+ T cell cytotoxicity in AMI patients. CONCLUSION: Up-regulation of MMP-2 might contribute to elevation of mCD100 shedding and sCD100 formation, leading to increased cytotoxicity CD8+ T cells in AMI patients.

Benchmark dose analysis of multiple genotoxicity endpoints in gpt delta mice exposed to aristolochic acid I.

As the carcinogenic risk of herbs containing aristolochic acids (AAs) is a global health issue, quantitative evaluation of toxicity is needed for the regulatory decision-making and risk assessment of AAs. In this study, we selected AA I (AAI), the most abundant and representative compound in AAs, to treat transgenic gpt delta mice at six gradient doses ranging from 0.125 to 4 mg/kg/day for 28 days. AAI-DNA adduct frequencies and gpt gene mutation frequencies (MFs) in the kidney, as well as Pig-a gene MFs and micronucleated reticulocytes (MN-RETs) frequencies in peripheral blood, were monitored. The dose-response (DR) relationship data for these in vivo genotoxicity endpoints were quantitatively evaluated using an advanced benchmark dose (BMD) approach with different critical effect sizes (CESs; i.e., BMD5, BMD10, BMD50 and BMD100). The results showed that the AAI-DNA adduct frequencies, gpt MFs and the MN-RETs presented good DR relationship to the administrated doses, and the corresponding BMDL100 (the lower 90% confidence interval of the BMD100) values were 0.017, 0.509 and 3.9 mg/kg/day, respectively. No positive responses were observed in the Pig-a MFs due to bone marrow suppression caused by AAI. Overall, we quantitatively evaluated the genotoxicity of AAI at low doses for multiple endpoints for the first time. Comparisons of BMD100 values across different endpoints provide a basis for the risk assessment and regulatory decision-making of AAs and are also valuable for understanding the genotoxicity mechanism of AAs.

Association of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles: a retrospective cohort study.

BACKGROUND: Parental body mass index (BMI) is associated with pregnancy outcomes. But the effect of parental prepregnancy BMI on offspring conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), especially the birth defect, remains to be determined. This study aimed to investigate the associations of parental prepregnancy BMI with neonatal outcomes and birth defect in fresh embryo transfer cycles. METHODS: We conducted a retrospective cohort study including 5741 couples in their first fresh IVF/ICSI cycles admitted to Women's Hospital, School of Medicine, Zhejiang University from January 2013 to July 2016. The primary outcome was birth defects, which was classified according to the International Classification of Diseases, 10th Revision. Secondary outcomes included preterm delivery rate, infant gender, birth weight, small-for-gestational age (SGA) and large-for-gestational age (LGA). Multilevel regression analyses were used to assess the associations of parental prepregnancy BMI with neonatal outcomes and birth defect. RESULTS: In singletons, couples with prepregnancy BMI ≥25 kg/m2 had higher odds of LGA than those with BMI < 25 kg/m2. The birth defect rate was significantly higher when paternal prepregnancy BMI ≥25 kg/m2 in IVF cycles (aOR 1.82, 95% CI 1.06-3.10) and maternal BMI ≥25 kg/m2 in ICSI cycles (aOR 4.89, 95% CI 1.45-16.53). For subcategories of birth defects, only the odds of congenital malformations of musculoskeletal system was significantly increased in IVF offspring with paternal BMI ≥25 kg/m2 (aOR 4.55, 95% CI 1.32-15.71). For twins, there was no significant difference among four groups, except for the lower birth weight of IVF female infants. CONCLUSIONS: Parental prepregnancy BMI ≥25 kg/m2 is associated with higher incidence of LGA in IVF/ICSI singletons. Paternal prepregnancy BMI ≥25 kg/m2 was likely to have higher risk of birth defect in IVF offspring than those with BMI < 25 kg/m2, particularly in the musculoskeletal system. It is essential for overweight or obesity couples to lose weight before IVF/ICSI treatments.

Aristolochic acid IVa forms DNA adducts in vitro but is non-genotoxic in vivo.

Aristolochic acids (AAs) are a family of natural compounds with AA I and AA II being known carcinogens, whose bioactivation causes DNA adducts formation. However, other congeners have rarely been investigated. This study aimed to investigate genotoxicity of AA IVa, which differs from AA I by a hydroxyl group, abundant in Aristolochiaceae plants. AA IVa reacted with 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) to form three dA and five dG adducts as identified by high-resolution mass spectrometry, among which two dA and three dG adducts were detected in reactions of AA IVa with calf thymus DNA (CT DNA). However, no DNA adducts were detected in the kidney, liver, and forestomach of orally dosed mice at 40 mg/kg/day for 2 days, and bone marrow micronucleus assay also yielded negative results. Pharmacokinetic analyses of metabolites in plasma indicated that AA IVa was mainly O-demethylated to produce a metabolite with two hydroxyl groups, probably facilitating its excretion. Meanwhile, no reduced metabolites were detected. The competitive reaction of AA I and AA IVa with CT DNA, with adducts levels varying with pH of reaction revealed that AA IVa was significantly less reactive than AA I, probably by hydroxyl deprotonation of AA IVa, which was explained by theoretical calculations for reaction barriers, energy levels of the molecular orbits, and charges at the reaction sites. In brief, although it could form DNA adducts in vitro, AA IVa was non-genotoxic in vivo, which was attributed to its low reactivity and biotransformation into an easily excreted metabolite rather than bioactivation.

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling.

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

Highly Selective Production of Ethylene by the Electroreduction of Carbon Monoxide.

Conversion of carbon monoxide to high value-added ethylene with high selectivity by traditional syngas conversion process is challenging because of the limitation of Anderson-Schulz-Flory distribution. Herein we report a direct electrocatalytic process for highly selective ethylene production from CO reduction with water over Cu catalysts at room temperature and ambient pressure. An unprecedented 52.7 % Faradaic efficiency of ethylene formation is achieved through optimization of cathode structure to facilitate CO diffusion at the surface of the electrode and Cu catalysts to enhance the C-C bond coupling. The highly selective ethylene production is almost without other carbon-based byproducts (e.g. C1 -C4 hydrocarbons and CO2 ) and avoids the drawbacks of the traditional Fischer-Tropsch process that always delivers undesired products. This study provides a new and promising strategy for highly selective production of ethylene from the abundant industrial CO.

An Adaption of Human-Induced Hepatocytes to In Vitro Genetic Toxicity Tests.

Metabolic activation is essential in standard in vitro genotoxicity test systems. At present, there is a lack of suitable cell models that can express the major characteristics of liver function for predicting substance toxicity in humans. Human-induced hepatocytes (hiHeps), which have been generated from fibroblasts by lentiviral expression of liver transcription factors, can express hepatic gene programs and can be expanded in vitro and display functional characteristics of mature hepatocytes, including cytochrome P450 enzyme activity and biliary drug clearance. Our purpose was to investigate whether hiHeps could be used as a more suitable model for genotoxicity evaluation of chemicals. Therefore, a direct mutagen, methylmethanesulfonate (MMS), and five promutagens [2-nitrofluorene (2-NF), benzo[a]pyrene (B[a]P), aflatoxin B1, cyclophosphamide and N-nitrosodiethylamine] were tested by the cytokinesis-block micronucleus test and the comet assay. Results from genotoxicity tests showed that the micronucleus frequencies were significantly increased by all of the six clastogens tested. Moreover, MMS, 2-NF and B[a]P induced significant increases in the % Tail DNA in the comet assay. In conclusion, our findings from the preliminary study demonstrated that hiHeps could detect the genotoxicity of indirect carcinogens, suggesting their potential to be applied as an effective tool for in vitro genotoxicity assessments.

Characterization of Charge Transfer in Excited States of Extended Clusters of π-Stacked Donor and Acceptor Complexes in Lock-Arm Supramolecular Ordering.

Lock-arm supramolecular ordering cocrystals formed by π-stacked materials constitute an interesting class of materials, which exhibits ferroelectric behavior at room temperature. To characterize the charge transfer in excited states, two complexes with π-stacked donors and acceptors, the 1,5-naphthalene diol (NDI) donor and pyromellitic diimide with diethylene glycol arms (PDIA) acceptor, 5-amino-1-naphthol (AMN) donor and PDIA acceptor, were investigated. The electronic excitations were calculated using the scaled opposite-spin variant of ADC(2), time-dependent density functional theory (TD-DFT) using a long-range corrected (LC) functional (ωB97xD), and the TD-LC approach within density-functional-based tight binding (TD-LC-DFTB). Face-to-face mixed stacks and edge-to-face crossed stacks up to hexamers were investigated. The calculations show that the ground state of the complexes does not possess significant CT character. On the other hand, the lowest excited state (S1) shows in all clusters a strong charge transfer. In several cases, the second excited state and also higher excited singlet states possess significant CT character. The orbitals involved in the excitation are mostly well localized and located on adjacent donor/acceptor pairs. Comparing different stacking directions, the vertical excitation energies for the NDI-PDIA crossed stacks are larger than those for the mixed stacks by 0.2-0.4 eV. In the case of the AMN-PDIA system, the energy differences are smaller (∼0.1 eV) with mostly the same energetic ordering as for the NDI-PDIA case. Strong red shifts in vertical fluorescence emission transitions have been computed, which could even lead to intersection between ground and first excited states, resulting in ultrafast radiationless decay and fluorescence quenching.

Anti-inflammatory Chalcone-Isoflavone Dimers and Chalcone Dimers from Caragana jubata.

Two new chalcone-isoflavone dimers, caraganins A (1) and B (2), two new chalcone dimers, caraganins C (3) and D (4), and eight known compounds (5-12) were obtained from the red heartwood of the rhizomes of Caragana jubata. The structures of caraganins A-D were established by 1D and 2D NMR spectroscopy, HRMS and ECD analysis, and comparison with previously known compounds. The anti-inflammatory activities of the new compounds were evaluated by measuring the production of NO, IL-6, and TNF-α in mouse RAW 264.7 macrophages induced by lipopolysaccharide. Among these, compounds 2 and 4 showed the most potent inhibitory activities (IC50: 4.1 and 5.2 µM, respectively) on nitric oxide formation, and compounds 1 and 4 displayed the most potent inhibitory activities on the secretion of inflammatory factor TNF-α, with IC50 values of 11.4 and 14.7 µM. The possible biosynthetic pathways of the chalcone-isoflavone dimers and the chalcone dimers are proposed.

Evaluation of HuoXueHuaYu therapy for nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trial.

BACKGROUND: To evaluate the effectiveness and safety of HuoXueHuaYu (HXHY) therapy in treating nonalcoholic fatty liver disease (NAFLD) through a systematic review and meta-analysis. METHODS: We performed comprehensive searches on Embase, Pubmed, Cochrane Library, CNKI, VIP and Wanfang databases up to June 2017 for randomized controlled trials using HXHY in the treatment of NAFLD compared with conventional treatment. RESULTS: This meta-analysis included 13 studies involving 1429 patients which 775 patients belonged to HXHY group and 654 patients belonged to conventional treatment group. The results of meta-analysis showed that HXHY can significantly improve B ultrasonic level (OR = 2.33; 95% CI:1.60, 3.40; P < 0.00001) of NAFLD compared with conventional treatment. As to lipids, HXHY was tested to be better on reduction of total cholesterol (TC) (MD = -0.38, 95% CI: - 0.48, - 0.29; P < 0.00001) and triglyceride (TG) (MD = -0.31; 95% CI: - 0.37, - 0.24; P < 0.00001) than conventional treatment. HXHY also had a greater beneficial effect on liver function in reducing alanine transaminase (ALT) (MD = -1.69; 95% CI: - 2.24, - 1.14; P < 0.00001) and aspartate transaminase (AST) (MD = -22.53; 95% CI: - 33.16, - 11.90; P < 0.00001) compared with conventional treatment. HXHY can also significantly improve the effective rate (OR = 3.55; 95% CI:2.65, 4.76; P < 0.00001) compared with conventional treatment. No serious adverse reactions were reported. CONCLUSIONS: HXHY seems to be an effective and safe therapy for NAFLD. It is suggested that further study of HXHY in the treatment of NAFLD requires trials with rigorous design, multicenter, large-scale and high-quality worldwide.

Effect of the Diabetic Environment On the Expression of MiRNAs in Endothelial Cells: Mir-149-5p Restoration Ameliorates the High Glucose-Induced Expression of TNF-α and ER Stress Markers.

BACKGROUND/AIMS: This study aimed to screen microRNAs and their corresponding target genes that are associated with vascular injury in type two diabetes mellitus (T2DM), investigate the effects of differentially expressed miRNAs and their target genes on high glucose-induced vascular injury and establish the mechanism underlying these effects. METHODS: A high-throughput digital gene expression (DGE) sequencing was performed to sequence microRNAs (miRNAs) and messenger RNAs (mRNAs) and determine their differential expression in human umbilical vein endothelial cells (HUVECs) incubated with serum samples from patients with T2DM and healthy volunteers. The HUVECs were transfected with si-TNF-α (tumor necrosis factor α) and a miR-149-5p inhibitor or mimic in vitro and then treated with normal or high glucose. The relative content of nitric oxide (NO) in the cells was detected using the Griess Reagent System. The mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were determined by qRT-PCR and Western blotting. The content of endothelin-1 (ET-1), von Willebrand factor (vWF), and intercellular adhesion molecular-1 (ICAM-1) were detected using an enzyme-linked immunosorbent assay (ELISA) kit. Apoptosis was determined by flow cytometry using the Annexin V/PI apoptosis detection kit. The mRNA and protein expression levels of ER stress (ERS) markers were determined by qRT-PCR and Western blotting. RESULTS: Based on the high-energy sequencing and in vitro pre-experiment studies, we determined that miR-149-5p and TNF-α were a differentially expressed mRNA/miRNA pair in T2DM with vascular injury. The luciferase reporter assay results demonstrated that miR-149-5p could directly target TNF-α. The upregulation of miR-149-5p reduced the high glucose-induced dysfunction in the HUVECs by significantly decreasing the levels of ET-1, vWF, and ICAM-1 and increasing the level of NO and the expression of eNOS. Additionally, we found that miR-149-5p can improve cell injury and reduce apoptosis by restoring the ameliorated high glucose-induced expression of ERS markers. CONCLUSION: TNF-α and miR-149-5p were differentially expressed in T2DM vascular endothelial injury. The over-expression of miR-149-5p ameliorates the high glucose-induced injury in the HUVECs by regulating the expression of TNF-α and ERS markers.

Tremella-like graphene-Au composites used for amperometric determination of dopamine.

Electrochemical detection of dopamine (DA) plays an important role in medical diagnosis. In this paper, tremella-like graphene-Au (t-GN-Au) composites were synthesized by a one-step hydrothermal method for selective detection of DA. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy were used to characterize as-prepared t-GN-Au composites. The t-GN-Au composites were directly used for the determination of DA via cyclic voltammetry (CV) and the chronoamperometry (CA) technique. CA measurement gave a wide linear range from 0.8 to 2000 µM, and the detection limit of 57 nM (S/N = 3) for DA. The mechanism and the heterogeneous electron transfer kinetics of the DA oxidation were discussed in the light of rotating disk electrode (RDE) experiments. Moreover, the modified electrode was applied to the determination of DA in human urine and serum samples.

Corticospinal tract: a new hope for the treatment of post-stroke spasticity.

Stroke is the third leading cause of death and disability worldwide. Post-stroke spasticity (PSS) is the most common complication of stroke but represents only one of the many manifestations of upper motor neuron syndrome. As an upper motor neuron, the corticospinal tract (CST) is the only direct descending motor pathway that innervates the spinal motor neurons and is closely related to the recovery of limb function in patients with PSS. Therefore, promoting axonal remodeling in the CST may help identify new therapeutic strategies for PSS. In this review, we outline the pathological mechanisms of PSS, specifically their relationship with CST, and therapeutic strategies for axonal regeneration of the CST after stroke. We found it to be closely associated with astroglial scarring produced by astrocyte activation and its secretion of neurotrophic factors, mainly after the onset of cerebral ischemia. We hope that this review offers insight into the relationship between CST and PSS and provides a basis for further studies.