Clinical algorithm model based on cfDNA to predict SLE disease activity.

BACKGROUND: Circulating cell-free DNA (cfDNA) has been widely used as a new liquid-biopsy marker. Dysregulation of cfDNA has been found in patients with systemic lupus erythematosus (SLE). However, the detailed association between cfDNA and SLE has not been thoroughly studied. METHODS: Plasma samples were collected from 88 patients with active SLE and 39 patients with inactive SLE. The cfDNA concentration was determined, and the length and distribution of cfDNA fragments were verified. RESULTS: cfDNA concentrations were significantly higher in patients with active SLE than in patients with inactive SLE (0.4 [0.18-0.897] ng/µL vs 0.249 [0.144-0.431] ng/µL; p = .043). cfDNA fragments were enriched in the ranges of 153-198 bp and 300-599 bp. cfDNA concentrations were associated with the reduction of the anti-double-stranded DNA (dsDNA) antibodies titer (r = -0.301, p = .034). The presence of anti-U1 ribonucleoprotein (p = .012), anti-Sjogren syndrome A (p = .024), anti-dsDNA (p = .0208), and anti-nucleosome antibodies (p = .0382) might associate to the variation of cfDNA concentration. Reduced cfDNA concentration was associated with renal damage in active SLE patients (0.31 [0.11-0.73] ng/µL vs 0.65 [0.27-1.53] ng/µL; p = .009). The Active index, a combination model including cfDNA concentration and other clinical indices, had an area of 0.886 under the receiver operating characteristics curve for distinguishing active SLE. The Active index was positively correlated with the SLE disease activity index score (r = 0.6724, p < .0001). CONCLUSIONS: Through systematic stratified analysis and clinical algorithm model, this study found that plasma cfDNA concentration is closely related to SLE disease severity, which has guiding significance for the future clinical application of cfDNA in SLE.

Current Progress in Treating Systemic Lupus Erythematosus Using Exosomes/MicroRNAs.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease associated with impaired organ functions that can seriously affect the daily life of patients. Recent SLE therapies frequently elicit adverse reactions and side effects in patients, and clinical heterogeneity is considerable. Mesenchymal stromal cells (MSCs) have anti-inflammatory, tissue repair, and immunomodulatory properties. Their ability to treat autoimmune diseases largely depends on secreted extracellular vesicles, especially exosomes. The effects of exosomes and microRNAs (miRNAs) on SLE have recently attracted interest. This review summarizes the applications of MSCs derived from bone marrow, adipocyte tissue, umbilical cord, synovial membrane, and gingival tissue, as well as exosomes to treating SLE and the key roles of miRNAs. The efficacy of MSCs infusion in SLE patients with impaired autologous MSCs are reviewed, and the potential of exosomes and their contents as drug delivery vectors for treating SLE and other autoimmune diseases in the future are briefly described.

Serological, fragmentomic, and epigenetic characteristics of cell-free DNA in patients with lupus nephritis.

Objectives: The biological characteristics of plasma circulating cell-free DNA (cfDNA) are related to the pathogenesis of lupus nephritis (LN). The aim of this study was to explore the biological characteristics of cfDNA in patients with LN in terms of serology, fragment omics, and epigenetics, and to discuss the possibility of liquid biopsy for cfDNA as an alternative to conventional tissue biopsy. Methods: cfDNA was extracted from plasma samples of 127 patients with systemic lupus erythematosus (64 with LN, 63 without LN). The cfDNA concentration was determined using the Qubit method. Next-generation sequencing cfDNA methylation profiling was performed for three LN patients and six non-LN patients. The methylation panel was designed based on data from The Cancer Genome Atlas cohort. The fragmentation index, motif score, and DELFI score were calculated to explore the fragmentation profile of cfDNA in patients with LN. Statistical and machine learning methods were used to select features to calculate the methylation scores of the samples. Results: Patients with LN had significantly lower cfDNA concentrations (P = 0.0347) than those without LN. This may be associated with the presence of anti-double-stranded DNA antibodies (r = -0.4189; P = 0.0296). The mean DELFI score (proportion of short fragments of cfDNA) in patients with LN was significantly higher than that in patients without LN (P = 0.0238). Based on the pan-cancer data, 73, 66, 8, and 10 features were selected and used to calculate the methylation scores. The mean methylation scores of these features in patients with LN differed significantly from those in patients without LN (P = 0.0238). Conclusions: The specificity of cfDNA in patients with LN was identified using serological, fragmentomic, and epigenetic analyses. The findings may have implications for the development of new molecular markers of LN.

Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review.

Objective: Rheumatoid arthritis (RA) is an autoimmune disorder. Multiple studies have investigated the risk of thyroid dysfunction in patients with RA but have reached conflicting conclusions. This systematic review aimed to determine whether patients with RA are at higher risk of thyroid dysfunction. Methods: We comprehensively reviewed online literature databases, including PubMed, Scopus, Embase, and the Cochrane Library, from their respective inception dates to March 25, 2022. Studies that provided data on at least one case of thyroid dysfunction in RA patients and their controls were included. Based on these data, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for thyroid dysfunction in RA and non-RA patients. Results: Twenty-nine studies met the inclusion criteria, involving a total of 35,708 patients with RA. The meta-analysis showed that, compared with non-RA patients, RA patients had an increased risk of developing thyroid dysfunction, particularly hypothyroidism (OR 2.25, 95% CI 1.78-2.84). Subgroup analysis suggested that study type and sample source of control group were the source of heterogeneity. Conclusions: Patients with RA are at increased risk of developing thyroid dysfunction, especially hypothyroidism. Routine biochemical examination of thyroid function in RA patients should be strengthened. Larger prospective studies are needed to explore the causal relationship between RA and thyroid dysfunction, and to investigate the impact of thyroid dysfunction on RA disease activity, drug efficacy, and medication safety. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022331142.

Assessment of breast lesions by the Kaiser score for differential diagnosis on MRI: the added value of ADC and machine learning modeling.

OBJECTIVES: To evaluate the diagnostic performance of Kaiser score (KS) adjusted with the apparent diffusion coefficient (ADC) (KS+) and machine learning (ML) modeling. METHODS: A dataset of 402 malignant and 257 benign lesions was identified. Two radiologists assigned the KS. If a lesion with KS > 4 had ADC > 1.4 × 10-3 mm2/s, the KS was reduced by 4 to become KS+. In order to consider the full spectrum of ADC as a continuous variable, the KS and ADC values were used to train diagnostic models using 5 ML algorithms. The performance was evaluated using the ROC analysis, compared by the DeLong test. The sensitivity, specificity, and accuracy achieved using the threshold of KS > 4, KS+ > 4, and ADC ≤ 1.4 × 10-3 mm2/s were obtained and compared by the McNemar test. RESULTS: The ROC curves of KS, KS+, and all ML models had comparable AUC in the range of 0.883-0.921, significantly higher than that of ADC (0.837, p < 0.0001). The KS had sensitivity = 97.3% and specificity = 59.1%; and the KS+ had sensitivity = 95.5% with significantly improved specificity to 68.5% (p < 0.0001). However, when setting at the same sensitivity of 97.3%, KS+ could not improve specificity. In ML analysis, the logistic regression model had the best performance. At sensitivity = 97.3% and specificity = 65.3%, i.e., compared to KS, 16 false-positives may be avoided without affecting true cancer diagnosis (p = 0.0015). CONCLUSION: Using dichotomized ADC to modify KS to KS+ can improve specificity, but at the price of lowered sensitivity. Machine learning algorithms may be applied to consider the ADC as a continuous variable to build more accurate diagnostic models. KEY POINTS: • When using ADC to modify the Kaiser score to KS+, the diagnostic specificity according to the results of two independent readers was improved by 9.4-9.7%, at the price of slightly degraded sensitivity by 1.5-1.8%, and overall had improved accuracy by 2.6-2.9%. • When the KS and the continuous ADC values were combined to train models by machine learning algorithms, the diagnostic specificity achieved by the logistic regression model could be significantly improved from 59.1 to 65.3% (p = 0.0015), while maintaining at the high sensitivity of KS = 97.3%, and thus, the results demonstrated the potential of ML modeling to further evaluate the contribution of ADC. • When setting the sensitivity at the same levels, the modified KS+ and the original KS have comparable specificity; therefore, KS+ with consideration of ADC may not offer much practical help, and the original KS without ADC remains as an excellent robust diagnostic method.

[Research advances on the effects of grazing on plant functional traits in grassland]. / æ”¾ç‰§å¯¹è‰åŽŸæ¤ç‰©åŠŸèƒ½æ€§çŠ¶å½±å“ç ”ç©¶è¿›å±•.

Plant functional traits is connected with vegetation adaptability to the environment. The trade-off between plant functional traits reflects resource reintegration and acquisition under grazing pressures. We summarized the differences of plant functional traits under grazing disturbance, focused on the linkages between grazing disturbance and plant functional traits. We introduced that the variation of plant functional traits resulted from the coordination between plant genetic characteristics and environmental filtration, summarized the effects of grazing on nutritional and reproductive traits, and noted that plants could use survival and reproductive strategies to adapt to the grazing disturbance. We mainly focused on the effects of grazing on plant population, community and ecosystem. The expression of plant functional traits was different under grazing disturbance. Therefore, plant functional traits could be used as indicators to explain population growth and reproduction, community assembly, and ecosystem function. In order to better serve the ecological environment of grassland with plant functional traits, reasonable grazing resis-tant species could be screened according to plant functional traits. Based on life history characteristics of grassland plant population, the scientific grazing mechanism should be formulated, and the responses of plant functional traits and resource allocation to grazing disturbance should be conducted from the perspective of individual-based level in the future.

Update on the role of extracellular vesicles in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder that leads to severe joint deformities, negatively affecting the patient's quality of life. Extracellular vesicles (EVs), which include exosomes and ectosomes, act as intercellular communication mediators in several physiological and pathological processes in various diseases including RA. In contrast, EVs secreted by mesenchymal stem cells perform an immunomodulatory function and stimulate cartilage repair, showing promising therapeutic results in animal models of RA. EVs from other sources, including dendritic cells, neutrophils and myeloid-derived suppressor cells, also influence the biological function of immune and joint cells. This review describes the role of EVs in the pathogenesis of RA and presents evidence supporting future studies on the therapeutic potential of EVs from different sources. This information will contribute to a better understanding of RA development, as well as a starting point for exploring cell-free-based therapies for RA.

Cannabinoid receptor agonist WIN55212-2 reduces unpredictable mild stress-induced depressive behavior of rats.

BACKGROUND: Depression is a neurological disorder characterized by persistent low mood. A number of studies have suggested that the use of type 1 cannabinoid receptor (CB1R) agonists can reduce depressive behavior, but its effect on the depressive behavior and nerve damage of rats exposed to chronic unpredictable mild stress (CUMS) has not been reported. METHODS: Rats were exposed to CUMS for 4 weeks to induce depressive behavior. Male Sprague-Dawley (SD) rats aged 6-8 weeks were randomly divided into six groups: control group (control), depression group (CUMS), depression + fluoxetine group (Flu), depression + WIN55212-2 group (WIN), depression + NF-κB inhibitor group (PDTC), and depression + WIN + PDTC group (WIN + PDTC). We performed four behavioral experiments test to evaluate the depressive behaviors of rats. Hematoxylin and eosin (HE) and Nissl staining were performed to observe the neuron structures of the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Biochemical experiments were performed to evaluate the concentrations of nitric oxide (NO), malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). Fluorescence quantitative PCR was used to detect the mRNA expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and inducible nitric oxide synthase (iNOS) in the hippocampus, and western blot was performed to detect protein expression levels related to the NF-κB signaling pathway in the hippocampus. RESULTS: Compared with the normal control group, CUMS significantly induced abnormal behaviors in stressed rats. The concentrations of pro-inflammatory factors and oxidative stress injury factors in the hippocampus of the CUMS group increased significantly. The interventions of Flu, WIN, and PDTC significantly reduced neuroinflammation and oxidative stress injury. Compared with the WIN group, the WIN + PDTC intervention group had better results. In addition, WIN could significantly inhibit the activation of the NF-κB signaling pathway. CONCLUSIONS: This study showed that cannabinoid receptor agonists can reduce the CUMS-induced depressive behaviors of rats by blocking the NF-κB signaling pathway to alleviate neuroinflammation and oxidative stress injury.

[Operation and Maintenance of Cost-Effective Volatile Organic Compounds Abatement Alternatives].

Presently, volatile organic compounds (VOCs) pollution control in China has entered the deep-water zone, facing difficult challenges. The cost-effectiveness of VOCs abatement alternatives will determine the final environmental benefits. Screening of abatement alternatives with good cost-effectiveness and performance is important to form a sound basis for VOCs emission abatement work to create sustainable and stable alternatives. In this study, 12 typical emission scenarios are set up based on the emission characteristics of pollution sources, such as emission concentration, airflow volume, continuous or intermittent emissions, and fluctuations in concentration. Based on these typical scenarios, the operation costs of current mainstream emission abatement alternatives is estimated, and a cost-effectiveness comparison is made using the unit abatement cost (UAC, yuan·kg-1, VOCs) as the index. The results obtained can provide a reference for choosing appropriate VOCs abatement alternatives according to the characteristics of VOCs emission. Results show that for low concentration VOCs, the UAC of emission abatement is normally more than 8 yuan·kg-1. The concentration in the process plays an important role in reducing UAC. Therefore, the reasonable collection of VOCs gas, resulting in smaller emission volume and higher concentration, has a significant impact on the subsequent emission abatement cost-effectiveness. Enhancing the classification collection of VOCs to improve resource attributes of the recovered VOCs liquid is also an effective way to improve the cost effectiveness of VOCs abatement.

Potential vectors of bluetongue virus in high altitude areas of Yunnan Province, China.

BACKGROUND: Bluetongue disease of ruminants is a typical insect-borne disease caused by bluetongue virus (BTV) of the genus Orbivirus (family Reoviridae) and transmitted by some species of Culicoides (Diptera: Ceratopogonidae). Recently, the detection of BTV in yaks in high altitude meadows of the Shangri-La district of Yunnan Province, China, prompted an investigation of the Culicoides fauna as potential vectors of BTV. METHODS: A total of 806 Culicoides midges were collected by light trapping at three sites at altitudes ranging from 1800 to 3300 m. The species were identified based on morphology and the DNA sequences of cytochrome c oxidase subunit 1 (cox1). PCR and quantitative PCR following reverse transcription were used to test for the presence of BTV RNA in Culicoides spp. A phylogenetic analysis was used to analyze the cox1 sequences of some specimens. RESULTS: Four species dominated these collections and cox1 barcoding revealed that at least two of these appear to belong to species new to science. Culicoides tainanus and a cryptic species morphologically similar to C. tainanus dominated low altitude valley collections while C. nielamensis was the most abundant species in the high-altitude meadow. A species related to C. obsoletus occurred at all altitudes but did not dominate any of the collections. BTV RT-qPCR analysis detected BTV RNA in two specimens of C. tainanus, in one specimen closely related to C. tainanus and in one specimen closely related to C. obsoletus by barcode sequencing. CONCLUSIONS: This study suggests that BTV in high altitude areas of Yunnan is being transmitted by three species of Culicoides, two of which appear to be new to science. This research may be useful in improving understanding of the effects of global warming on arboviral disease epidemiology and further study is important in research into disease control and prevention.

The serologic investigation and viral isolation of bluetongue virus in Shangri-La in Southwest China.

Bluetongue is an arthropod-borne viral disease of ruminants caused by bluetongue virus (BTV). In China, BTV is relatively common in Yunnan Province with the exception of northern regions around Shangri-La, where the average altitude is approximately 3,450 metres. Recently, the seroprevalence of BTV has been measured in yaks in Shangri-La; therefore, this study investigated BTV infections in this area. The serological investigation in five villages in Shangri-La showed that there were sporadic BTV infections in yaks (20 of 507 positive) during 2014 to 2017, while the seroprevalence of BTV at three goat farms in a nearby river valley was 35%-65% in 2017. Subsequently, 20 sentinel goats were kept on two separate farms in the river valley and monitored for seroconversion between May and September of 2017. Five of the sentinel animals were tested positive for antibodies to BTV by C-ELISA during the study period, and 13 BTV isolates were isolated from ten sentinel animals. All isolates were identified as the same serotype, and the complete nucleotide sequence of one was determined. The genomic sequences showed that the isolated BTV strain belonged to serotype 21 and had approximately 99.8%-100% homology with three Indonesian BTV-21 strains (D151, RIVS-66 and RIVS-60) between their coding sequences (CDSs) except for Seg4 (99.5%). Besides, our data suggested that this BTV-21 strain might have also infected some local yaks and sheep.

How wastewater with different nutrient levels influences microbial degradation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in anaerobic sediments.

While wastewater and polybrominated diphenyl ethers (PBDEs) are commonly both discharged into aquatic ecosystems, little information is known about how wastewaters with different nutrient levels impact on microbial degradation of PBDEs. In this study, we used an anaerobic microcosm experiment to examine how the removal rates of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) from contaminated sediment varied when exposed to three wastewaters with different nutrient properties, namely livestock wastewater (LS), municipal sewage (MS), and shrimp pond wastewater (SP), and to determine the microbial controls on removal processes. We found that BDE-47 degraded relatively rapidly in MS, which had low carbon and nitrogen concentrations, but degraded much more slowly in LS and SP, which had relatively high nutrient concentrations. The variations in BDE-47 removal in different wastewater were related to iron reduction rates and the abundances of organohalide-respiring bacteria (OHRB). The community compositions of both total bacteria and OHRB from the family Dehalococcoidaceae differed significantly among the wastewater treatments. Compared with other treatments, some bacterial groups with PBDE degradation abilities were more abundant in MS where the PBDE-degradation efficiencies were higher. Our results should help support evaluations of the bioremediation potential of sites that are contaminated with both halogenated organic compounds and nutrient-rich wastewater.

Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography.

Osteoporosis or osteopenia is a common complication in patients with cirrhosis, but little is known about the risk factors for the occurrence of osteoporosis.Patients with liver cirrhosis due to chronic virus infection and alcoholic abuse were enrolled. Bone mineral density (BMD) was determined using dual-energy x-ray absorptiometry (DXA). Osteoporosis was diagnosed according to WHO criteria. The severity of liver stiffness was measured by Fibroscan. Demographic data, such as age, gender, weight, height, and body mass index (BMI), were collected. Logistic regression analysis was used to recognize the risk factors of osteoporosis in patients with cirrhosis.A total of 446 patients were included in this study: 217 had liver cirrhosis (male, 74.2%; mean age, 57.2 ±â€Š10.27) and 229 were matched controls (male, 69%, mean age, 56.69 ±â€Š9.37). Osteoporosis was found in 44 patients (44/217, 20.3%). The spine and hip BMD in cirrhotic patients were significantly lower than that in controls. When the cirrhotic and control subjects were stratified by age, gender, and BMI, the significant difference was also observed in women patients, patients older than 60, and patients with BMI < 18. Multivariate analysis showed that the older age [odds ratio (OR) = 1.78, P = .046], lower BMI (OR = 0.63, P = .049), greater fibroscan score (OR = 1.15, P = .009), and liver cirrhosis induced by alcohol liver disease (OR = 3.42, P < .001) were independently associated with osteoporosis in cirrhotic patients.Osteoporosis occurred in about one-fifth of patients with liver cirrhosis, which was associated with age, BMI, Fibroscan score, and alcohol liver disease related liver cirrhosis.

[Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicines].

Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicine. The patients were divided into two groups： the simple Western medicine treatment group (control group) and the traditional Chinese medicine and Western medicine treatment group (treatment group). The patients in the two groups were treated with conventional western medicine.The treatment group was given based on Buxin Yishen decoction, a total of three courses of treatment to observe the two groups of patients before and after treatment of total efficacy, cardiac function indicators, changes in renal function indicators. The total efficacy of the treatment group and the control group were 91.80% and 72.41%, respectively. There were significant differences between the two groups (P<0.01). The cardiac function indexes and renal function indexes of the treatment group and the control group before and after treatment (P<0.01). Compared with the two groups, the left ventricular function, Hematuria natriuretic peptide, serum creatinine, urea nitrogen, cystatin-C were improved, and the treatment group (P<0.05~0.01). The results showed that the combination of traditional Chinese and Western medicine treatment can improve the clinical efficacy of type 2 heart and kidney syndrome, significantly improve heart and kidney function, better than conventional Western medicine treatment, and has good safety.

CLD1/SRL1 modulates leaf rolling by affecting cell wall formation, epidermis integrity and water homeostasis in rice.

Leaf rolling is considered as one of the most important agronomic traits in rice breeding. It has been previously reported that SEMI-ROLLED LEAF 1 (SRL1) modulates leaf rolling by regulating the formation of bulliform cells in rice (Oryza sativa); however, the regulatory mechanism underlying SRL1 has yet to be further elucidated. Here, we report the functional characterization of a novel leaf-rolling mutant, curled leaf and dwarf 1 (cld1), with multiple morphological defects. Map-based cloning revealed that CLD1 is allelic with SRL1, and loses function in cld1 through DNA methylation. CLD1/SRL1 encodes a glycophosphatidylinositol (GPI)-anchored membrane protein that modulates leaf rolling and other aspects of rice growth and development. The cld1 mutant exhibits significant decreases in cellulose and lignin contents in secondary cell walls of leaves, indicating that the loss of function of CLD1/SRL1 affects cell wall formation. Furthermore, the loss of CLD1/SRL1 function leads to defective leaf epidermis such as bulliform-like epidermal cells. The defects in leaf epidermis decrease the water-retaining capacity and lead to water deficits in cld1 leaves, which contribute to the main cause of leaf rolling. As a result of the more rapid water loss and lower water content in leaves, cld1 exhibits reduced drought tolerance. Accordingly, the loss of CLD1/SRL1 function causes abnormal expression of genes and proteins associated with cell wall formation, cuticle development and water stress. Taken together, these findings suggest that the functional roles of CLD1/SRL1 in leaf-rolling regulation are closely related to the maintenance of cell wall formation, epidermal integrity and water homeostasis.

Leptocarpin Suppresses Proliferation, Migration, and Invasion of Human Osteosarcoma by Targeting Type-1 Insulin-Like Growth Factor Receptor (IGF-1R).

BACKGROUND Leptocarpin (LTC) has drawn much attention for suppressing tumor growth or reducing inflammation. However, the effect of LTC on osteosarcoma has rarely been reported. Our object was to determine whether LTC suppresses MG63 cell proliferation, migration, and invasion, and whether type-1 insulin-like growth factor receptor (IGF-1R) is one of the targets in LTC suppressing osteosarcoma. MATERIAL AND METHODS Cytotoxicity of LTC was performed by use of a cell-counting kit-8 (CCK-8). RNA interference (RNAi) or pEABE-bleo IGF-1R plasmid were used for silencing or overexpressing IGF-1R, Western blot (WB) analysis was used for IGF-1R expression, CCK-8 for proliferation, and transwell assay for migration and invasion. RESULTS LTC (23.533 µM) treatment for 48 h was taken as the 50% inhibiting concentration (IC50), which significantly (P<0.05) suppressed MG63 cells proliferation, migration, and invasion. LTC (IC50) obviously inhibited IGF-1R expression in MG63 cells, with similar effect to small interfering RNA (siRNA), while pEABE-bleo IGF-1R transfection overexpressed IGF-1R. siRNA silencing IGF-1R suppressed MG63 cells proliferation, migration, and invasion, while pEABE-bleo IGF-1R transfection was significantly (P<0.05) promoted. With or without siRNA or pEABE-bleo IGF-1R transfection, LTC (IC50) suppressed MG63 cells proliferation, migration, and invasion. The effect of LTC (IC50) combined with siRNA on suppressing MG63 cells proliferation, migration, and invasion was more obvious, while the effect of LTC (IC50) combined with pEABE-bleo IGF-1R transfection was less significant (P<0.05). CONCLUSIONS LTC suppressed osteosarcoma proliferation, migration, and invasion by inhibiting IGF-1R expression. IGF-1R is one of the targets in LTC suppressing osteosarcoma.

Bioequivalence of two oseltamivir formulations in healthy Chinese volunteers
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BACKGROUND: The aim of this study was to compare the bioavailability of a new generic formulation of oseltamivir 75-mg capsule (test) and a branded formulation Tamiflu® (reference) to meet regulatory criteria for marketing the test product in healthy Chinese male volunteers. METHODS: This single-dose, randomized-sequence, open-label, two-period crossover study was conducted in fasted healthy Chinese male volunteers, who first received a single oral dose of the test or reference formulation with a 7-day washout period, and then the alternative formulation. The study drug was administered after a 10-hour overnight fast. Blood samples were collected at baseline and at 0.25, 0.5, 0.75, 1.0, 1.5, 2, 4, 6, 8, 10, 12, 24, and 36 hours after administration of the study drug. Plasma concentrations of the parent oseltamivir and its metabolite oseltamivir carboxylate were determined using an LC-MS/MS method. The formulations were considered bioequivalent if the 90% confidence intervals (CIs) for the log-transformed values were within the predetermined equivalence range (70 - 143% for Cmax, 80 - 125% for AUC) according to the guidelines of the State Food and Drug Administration of China. Adverse events (AEs) were monitored throughout the study based on clinical parameters and patient reports. RESULTS: Characteristics of the 20 male volunteers included were as follows: mean age 23 (± 0.7, SD) years (range 21 - 24 years); weight 69 (± 7.1) kg (range 60 - 88 kg); height 177 (± 5.9) cm (range 168 - 192 cm). All included subjects completed the study. The mean geometric ratio between the test and reference formulations of oseltamivir was 99.5% (90% CI), 86.3 - 114.8%) for Cmax, 104.4% (95.7 - 113.9%) for AUC0-t, and 104.4% (95.6 - 113.9%) for AUC0-∞. That of oseltamivir carboxylate was 103.7% (90% CI, 95.3 - 112.8%) for Cmax, 101.7% (96.6 - 107.1%) for AUC0-t, and 101.4% (96.5 - 106.5%) for AUC0-∞. There was no significant difference in pharmacokinetic parameters between the two groups. Only 1 AE (nausea) occurred in 1 subject who received the test formulation; the AE resolved without any treatment. CONCLUSIONS: The result of this single-dose study indicated that the test formulation of oseltamivir capsule met the Chinese regulatory criteria for bioequivalence vs. the reference formulation in fasted healthy Chinese male volunteers.
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Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicines / 中国中药杂志

Clinical observation on treatment of type 2 cardiac and kidney syndrome by combination of traditional Chinese and Western medicine. The patients were divided into two groups： the simple Western medicine treatment group (control group) and the traditional Chinese medicine and Western medicine treatment group (treatment group). The patients in the two groups were treated with conventional western medicine.The treatment group was given based on Buxin Yishen decoction, a total of three courses of treatment to observe the two groups of patients before and after treatment of total efficacy, cardiac function indicators, changes in renal function indicators. The total efficacy of the treatment group and the control group were 91.80% and 72.41%, respectively. There were significant differences between the two groups (P<0.01). The cardiac function indexes and renal function indexes of the treatment group and the control group before and after treatment (P<0.01). Compared with the two groups, the left ventricular function, Hematuria natriuretic peptide, serum creatinine, urea nitrogen, cystatin-C were improved, and the treatment group (P<0.05~0.01). The results showed that the combination of traditional Chinese and Western medicine treatment can improve the clinical efficacy of type 2 heart and kidney syndrome, significantly improve heart and kidney function, better than conventional Western medicine treatment, and has good safety.

REL2, A Gene Encoding An Unknown Function Protein which Contains DUF630 and DUF632 Domains Controls Leaf Rolling in Rice.

BACKGROUND: Rice leaves are important energy source for the whole plant. An optimal structure will be beneficial for rice leaves to capture light energy and exchange gas, thus increasing the yield of rice. Moderate leaf rolling and relatively erect plant architecture may contribute to high yield of rice, but the relevant molecular mechanism remains unclear. RESULTS: In this study, we identified and characterized a rolling and erect leaf mutant in rice and named it as rel2. Histological analysis showed that the rel2 mutant has increased number of bulliform cells and reduced size of middle bulliform cells. We firstly mapped REL2 to a 35-kb physical region of chromosome 10 by map-based cloning strategy. Further analysis revealed that REL2 encodes a protein containing DUF630 and DUF632 domains. In rel2 mutant, the mutation of two nucleotide substitutions in DUF630 domain led to the loss-of-function of REL2 locus and the function of REL2 could be confirmed by complementary expression of REL2 in rel2 mutant. Further studies showed that REL2 protein is mainly distributed along the plasma membrane of cells and the REL2 gene is relatively higher expressed in younger leaves of rice. The results from quantitative RT-PCR analysis indicated that REL2 functioning in the leaf shape formation might have functional linkage with many genes associated with the bulliform cells development, auxin synthesis and transport, etc. CONCLUSIONS: REL2 is the DUF domains contained protein which involves in the control of leaf rolling in rice. It is the plasma membrane localization and its functions in the control of leaf morphology might involve in multiple biological processes such as bulliform cell development and auxin synthesis and transport.

Comprehensive Genomic Analysis and Expression Profiling of the NOX Gene Families under Abiotic Stresses and Hormones in Plants.

Plasma membrane NADPH oxidases (NOXs) are key producers of reactive oxygen species under both normal and stress conditions in plants and they form functional subfamilies. Studies of these subfamilies indicated that they show considerable evolutionary selection. We performed a comparative genomic analysis that identified 50 ferric reduction oxidases (FRO) and 77 NOX gene homologs from 20 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots, and eudicots. Phylogenetic and structural analysis classified these FRO and NOX genes into four well-conserved groups represented as NOX, FRO I, FRO II, and FRO III. Further analysis of NOXs of phylogenetic and exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures during the evolution of NOXs family genes and which were classified into four conserved subfamilies which are represented as Sub.I, Sub.II, Sub.III, and Sub.IV. Additionally, both available global microarray data analysis and quantitative real-time PCR experiments revealed that the NOX genes in Arabidopsis and rice (Oryza sativa) have different expression patterns in different developmental stages, various abiotic stresses and hormone treatments. Finally, coexpression network analysis of NOX genes in Arabidopsis and rice revealed that NOXs have significantly correlated expression profiles with genes which are involved in plants metabolic and resistance progresses. All these results suggest that NOX family underscores the functional diversity and divergence in plants. This finding will facilitate further studies of the NOX family and provide valuable information for functional validation of this family in plants.