Adjuvant role of Salvia miltiorrhiza bunge in cancer chemotherapy: A review of its bioactive components, health-promotion effect and mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy is a common cancer treatment strategy. However, its effectiveness is constrained by toxicity and adverse effects. The Lamiaceae herb Salvia miltiorrhiza Bunge has a long history of therapeutic use in the treatment of blood stasis illnesses, which are believed by traditional Chinese medicine to be connected to cancer. AIM OF THE STUDY: This review summarized the common toxicity of chemotherapy and the potential chemo-adjuvant effect and mechanisms of active ingredients from S. miltiorrhiza, hoping to provide valuable information for the development and application of S. miltiorrhiza resources. MATERIALS AND METHODS: The literatures were retrieved from PubMed, Web of Science, Baidu Scholar and Google Scholar databases from 2002 to 2022. The inclusion criteria were studies reporting that S. miltiorrhiza or its constituents enhanced the efficiency of chemotherapy drugs or reduced the side effects. RESULTS: Salvianolic acid A, salvianolic acid B, salvianolic acid C, rosmarinic acid, tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I and miltirone are the primary adjuvant chemotherapy components of S. miltiorrhiza. The mechanisms mainly involve inhibiting proliferation, metastasis, and angiogenesis, inducing apoptosis, regulating autophagy and tumor microenvironment. In addition, they also improve chemotherapy drug-induced side effects. CONCLUSIONS: The bioactive compounds of S. miltiorrhiza are shown to inhibit proliferation, metastasis, and angiogenesis, induce apoptosis and autophagy, regulate immunity and tumor microenvironment when combined with chemotherapy drugs. However, further clinical studies are required to validate the current studies.

Acute cold stress leads to zebrafish ovarian dysfunction by regulating miRNA and mRNA.

Temperature is a critical factor that regulates the reproduction processes in teleost. However, the gonadal response mechanism to cold stress in fish remains largely unknown. In the present study, female zebrafish were exposed to different extents of low temperatures at 18 °C and 10 °C for 48 h. The ovarian histology was remarkably damaged after cold stress exposure. Integrated analysis of miRNA-mRNA was used to investigate the ovarian response to acute cold stress. A large number of mRNAs and miRNAs were altered by cold stress, which are involved in extensive biological processes. It is indicated that the signal transduction of MAPK and Calcium signaling pathway is highly engaged in zebrafish ovary to adapt to cold stress. The immune system was dysregulated by cold stress while the ovarian autophagy was activated. Remarkably increased gene number related to reproductive functions was identified in the cold stress at 10 °C compared to the control. The cold stress-induced dysregulated reproductive genes include star, hsd3b1, hsd17b1, inha, insl3, amh, nanos1 and foxl2. Combined with the dysregulated insulin, IGF and progesterone signaling, it is suggested that cold stress affects ovarian function in multiple aspects, including oocyte meiosis, folliculogenesis, final maturation and ovarian maintenance. On the other hand, the ovarian miRNA-mRNA regulatory network response to cold stress was also constructed. Overall, our result revealed the ovarian response to cold stress in zebrafish and provided insight into the fish adaptation mechanism to acute temperature change.

Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2-/-) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2-/- mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2-/- mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2-/- mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2-/- mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2-/- mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

Treatment of refractory or relapsed myelodysplastic neoplasms with luspatercept: a multicenter Chinese study.

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67 years: range 29 to 80 years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9 weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8 weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84 g/L, and patients had significantly higher hemoglobin concentrations after 12 weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500 IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity.

OBJECTIVE: Islet α cells input is essential for insulin secretion from ß cells. The present study aims to investigate the association between 25-hydroxyvitamin D [25(OH)D] and islet function homeostasis in type-2 diabetes (T2D) patients. METHODS: A total of 4670 T2D patients from seven communities in Shanghai, China were enrolled. The anthropometric indices, biochemical parameters, serum 25(OH)D, and islet function [including C-peptide (C-p) and glucagon] were measured. RESULTS: The fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), glucagon, and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased. Next, the population was divided into two groups: abdominal obesity and non-abdominal obesity groups. After adjustment, the 25(OH)D level was found to be associated with HbA1c, glucagon, and homeostasis model assessment of ß (HOMA-ß) in the non-abdominal obesity group. There was a significant relationship between 25(OH)D and HbA1c, glucagon, HOMA-IR, baseline insulin or C-p in the abdominal obesity group. In the abdominal obesity group, the ordinary least squares (OLS) regression and quantile regression revealed that 25(OH) D was obviously associated with glucagon and fasting C-p levels. In the abdominal obesity group, the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p (P=0.0124). Furthermore, the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation (SD) below the mean (P=0.0002), and lower at the mean of the course of diabetes (P=0.0007). CONCLUSION: 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity. The 25(OH)D influenced C-p in part by influencing glucagon. The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity, in terms of islet homeostasis, is influenced by the course of diabetes.

Effects of light environments within Cinnamomum camphora canopy on leaf functional traits and photosynthetic characteristics.

To explore the adaptive mechanism of leaf photosynthetic capacity in different light environments within Cinnamomum camphora canopy and enhance carbon sequestration, we investigated morphological structures, nutritional and physiological traits and photosynthetic characteristics of leaves in different orientations of C. camphora canopy, southern side in the outer layer (100% full light), southern side in the inner layer (34% full light) and northern side (21% full light). We analyzed the main limitation resulting in down-regulation of photosynthetic capacity in low light environments. Results showed that specific leaf weight, the thickness of lower and upper epidermal cuticle, lower epidermis, palisade tissue as well as cell number and width of palisade tissue, the thickness ratio of palisade to spongy tissue, cell structure closely degree significantly decreased with decreasing light intensity within canopy, opposite to the responses of spongy tissue thickness, cell length-width ratio of palisade tissue, and cell structure loose degree. The contents of leaf carbon, soluble protein, soluble sugar and starch were significantly lower in two low light environments compared with full light, whereas nitrogen content was markedly higher in north side. Low light prominently reduced gas exchange parameters, i.e., net photosynthetic rate (Pn), dark respiration rate, stomatal conductance to CO2(gsc), mesophyll conductance to CO2(gm), total conductance to CO2(gtot), intercellular CO2 concentration (Ci), CO2 concentration at the chloroplast (Cc). Pn was positively correlated with gsc, gm, gtot and Cc. There were no differences in maximum quantum photochemical efficiency, actual quantum photochemical efficiency, photochemical quenching coefficient, maximum rate of Rubisco carboxylation (Vc max) and maximum rate of electron transport (Jmax) among light environments. Vc max and Jmax were positively correlated to Pn. Of the shading-induced limitations to photosynthesis, gm limitation was the most important, and gsc limitation was enhanced with further weakened light intensity while biochemical limitation was rather limited. In summary, the results suggested that full light could improve leaf photosynthetic potential in C. camphora canopy leaves, reduce the effects of gm and gsc limitation on photosynthesis, and consequently enhance carbon assimilation capacity.

Anti-Allergic and Anti-inflammatory Effects of Bakuchiol on Ovalbumin-Induced Allergic Rhinitis in Mice.

Allergic rhinitis (AR) is a prevalent inflammatory disease primarily affecting the nasal mucosa and is caused by allergies. The common symptoms of AR include rhinorrhea, sneezing, itchy nose, congestion, teary eyes, and nasal rubbings. The present study assessed the beneficial properties of bakuchiol on OVA-induced AR in mice via the regulation of inflammatory responses. AR was induced by injecting (i.p.) OVA (50 µg) and aluminum hydroxide (1 mg) into mice at various time intervals. The bakuchiol treatment was done at dosages of 10 and 20 mg/kg with dexamethasone (2.5 mg/kg) as a positive control. The body weight and nasal symptoms were measured on the day of the last OVA challenge. For in vitro tests, mouse splenocytes were isolated, sensitized with 20 µL OVA, and then treated with 10 µM bakuchiol. The levels of pro-inflammatory cytokines, immunoglobulins, histamine, leukotriene C4 (LTC-4), and prostaglandin D2 (PGD2) were assayed using the corresponding assay kits. The assay kits were also used to analyze the status of oxidative stress markers. The Th1/Th2 cell proportion was assessed using flow cytometry. The bakuchiol (10 and 20 mg/kg) treatment reduced the nasal symptoms in AR mice. Bakuchiol decreased the levels of IL-4, IL-5, IL-13, Igs (IgE and IgG1), histamine, IL-10, IL-33, and TNF-α in AR mice. Bakuchiol also reduced PGDA and LTC-4 levels in the NLF of AR mice. The ROS and MDA levels were decreased, whereas boosted SOD activity was observed in the bakuchiol-treated AR mice. The eosinophil count was decreased in the nasal tissues of bakuchiol-treated AR mice. Bakuchiol also influenced the Th1 and Th2 cell proportions in AR mice. The present findings suggest that bakuchiol is effective against OVA-mediated allergic and inflammatory responses in AR mice through its strong anti-inflammatory properties.

Natural reference structures for three-dimensional maxillary regional superimposition in growing patients.

BACKGROUND: Assessment of growth-related or treatment-related changes in the maxilla requires a reliable method of superimposition. Such methods are well established for two-dimensional (2D) cephalometric images but not yet for three-dimensions (3D). The aims of this study were to identify natural reference structures (NRS) for the maxilla in growing patients in 3D, opportunistically using orthodontic mini-screws as reference; and to test the applicability of the proposed NRS for maxillary superimposition by assessing the concordance of this approach with Björk's 'stable reference structures' in lateral projection. METHODS: The stability of the mini-screws was tested on longitudinal pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images by measuring the distance changes between screws. After verifying the stability of the mini-screws, rigid registration was performed for aligning the stable mini-screws. Then, non-rigid registration was used to establish the dense voxel-correspondence among CBCT images and calculate the displacement of each voxel belonging to the maxilla relative to the mini-screws. The displacement vectors were transformed to a standardized maxillary template to categorize the stability of the internal structures statistically. Those voxels that displaced less relative to the mini-screws were considered as the natural reference structures (NRS) for the maxilla. Test samples included another dataset of longitudinal CBCT scans. They were used to evaluate the applicability of the proposed NRS for maxillary superimposition. We assessed whether aligning the maxilla with proposed NRS is in concordance with the maxillary internal reference structures superimposition in the traditional 2D lateral view as suggested by Björk. This was quantitively assessed by comparing the mean sagittal and vertical tooth movements for both superimposition methods. RESULTS: The stability of the mini-screws was tested on 10 pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images (T1: 12.9 ± 0.8 yrs, T2: 14.8 ± 0.7 yrs). Both the loaded and the unloaded mini-screws were shown to be stable during orthodontic treatment, which indicates that they can be used as reference points. By analyzing the deformation map of the maxilla, we confirmed that the infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than  1 cm distal to incisor foramen except the palatal suture) were stable during growth. Another dataset of longitudinal CBCT scans (T1: 12.2 ± 0.63 yrs, T2: 15.2 ± 0.96 yrs) was used to assess the concordance of this approach with Björk's 'stable reference structures'. The movement of the maxillary first molar and central incisor showed no statistically significant difference when superimposing the test images with the proposed NRS or with the classic Björk maxillary superimposition in the lateral view. CONCLUSIONS: The infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm posterior to incisal foramen except the palatal suture) were identified as stable regions in the maxilla. These stable structures can be used for maxillary superimposition in 3D and generate comparable results to Björk superimposition in the lateral view.

Prophylactic Effects of Hemp Seed Oil on Perimenopausal Depression: A Role of HPA Axis.

Hemp seed, the dried fruit of Cannabis sativa L. (Moraceae), has been extensively documented as a folk source of food due to its nutritional and functional value. This study evaluated the antidepressant effect of hemp seed oil (HSO) during its estrogen-like effect in Perimenopausal depression (PMD) rats induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Female SD rats (SPF, 10 weeks, sham operated group, ovariectomy (OVX) model group, ovariectomy - chronic unpredictable mild stress (OVX-CUMS) group, HSO + OVX-CUMS group, fluoxetine (FLU) + OVX-CUMS group, n=8) were subjected to treatment with HSO (4.32 g/kg) or fluoxetine (10 mg/kg) for 28 days (20 mL/kg by ig). Sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), estrogen receptor α (ERα) and estrogen receptor ß (ERß) expression, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol (CORT), adrenocorticotropic hormone (ACTH), corticotropin releasing hormone (CRH), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels are measured to evaluate the function of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-adrenal (HPA) axis. The results showed that OVX-CUMS significantly decrease sucrose preference rate in SPT, increase immobility time in FST and OFT, and decrease movement distance and stand-up times in OFT. HSO treatment significantly improves depression-like behaviors, upregulates the expression of ERα and ERß, improves HPO axis function by increasing E2 levels and decreasing FSH and LH levels, reverses HPA axis hyperactivation by decreasing CORT, ACTH, and CRH levels, and upregulates NE, 5-HT, and 5HIAA levels in model rats. The findings suggested that HSO could improve depression-like behavior in OVX-CUMS rats by regulating HPO/HPA axis function and neurotransmitter disturbance.

Dynamics of imprinted genes and their epigenetic mechanisms in castor bean seed with persistent endosperm.

Genomic imprinting refers to parent-of-origin-dependent gene expression and primarily occurs in the endosperm of flowering plants, but its functions and epigenetic mechanisms remain to be elucidated in eudicots. Castor bean, a eudicot with large and persistent endosperm, provides an excellent system for studying the imprinting. Here, we identified 131 imprinted genes in developing endosperms and endosperm at seed germination phase of castor bean, involving into the endosperm development, accumulation of storage compounds and specially seed germination. Our results showed that the transcriptional repression of maternal allele of DNA METHYLTRANSFERASE 1 (MET1) may be required for maternal genome demethylation in the endosperm. DNA methylation analysis showed that only a small fraction of imprinted genes was associated with allele-specific DNA methylation, and most of them were closely associated with constitutively unmethylated regions (UMRs), suggesting a limited role for DNA methylation in controlling genomic imprinting. Instead, histone modifications can be asymmetrically deposited in maternal and paternal genomes in a DNA methylation-independent manner to control expression of most imprinted genes. These results expanded our understanding of the occurrence and biological functions of imprinted genes and showed the evolutionary flexibility of the imprinting machinery and mechanisms in plants.

Comparison of eltrombopag and avatrombopag in the treatment of refractory/relapsed aplastic anemia: a single-center retrospective study in China.

Background: Eltrombopag (ELT), a thrombopoietin receptor agonist (TPO-RA), has been approved for relapsed/refractory aplastic anemia (AA). However, data on avatrombopag (AVA), another TPO-RA, are limited, and the comparisons between the two TPO-RAs are lacking. Objectives: We aimed to compare the efficacy and safety between ELT and AVA in relapsed/refractory AA patients. Design: In this retrospective study, patients with relapsed/refractory AA who had been treated with ELT (N = 45) or AVA (N = 30) alone and had compatible baseline hematological parameters were compared. Methods: Data from patients diagnosed with acquired AA were retrospectively collected. All patients were refractory/relapsed to standard immunosuppressive therapy (IST) for at least 6 months before ELT or AVA. Patients had to be treated with ELT or AVA alone for at least 6 months before evaluation if they did not respond. Baseline characteristics, overall response (OR), complete response (CR), relapse, adverse events, and factors that may affect efficacy were analyzed. Results: Of the 75 patients enrolled, 45 received ELT and 30 received AVA. Patients with AVA had a higher percentage of abnormal liver or renal function than those with ELT (p = 0.036). No significant difference was found in the OR/CR rate in the first/second/third/sixth month between the two cohorts (p > 0.05). Patients treated with AVA had a shorter median time to response than those treated with ELT (p = 0.012) and had a higher platelet level in the second month (p = 0.041). AVA had fewer adverse events than ELT (p = 0.046). Under compatible follow-up time (p = 0.463), no difference was found between the ELT and AVA cohorts in relapse (p = 1.000) or clone evolution (p = 0.637). No predictive factors for OR and CR in the sixth month were found for either ELT or AVA. Conclusion: With worse liver or renal function, AVA had a similar OR/CR rate but a shorter median time to response and fewer adverse events for patients with relapsed/refractory AA.

Combined Aerobic and Resistance Exercise Interventions for Children and Adolescents With Cancer: A Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Systematic reviews in adults with cancer have shown the benefits of combined aerobic and resistance exercise (CE) interventions on physical and psychological fitness. However, data on the efficacy of CE interventions for children and adolescents are limited and discordant. LITERATURE SEARCH: The PubMed®, Embase®, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure electronic databases were searched from inception to April 19, 2022. DATA EVALUATION: Nine randomized controlled trials met the inclusion criteria. A quantitative synthesis method was used to investigate the effects of CE interventions on fatigue, cardiorespiratory fitness, physical activity levels, and health-related quality of life. SYNTHESIS: This systematic review and meta-analysis indicates that CE interventions have beneficial effects on the fatigue, cardiorespiratory fitness, and physical activity levels of this population. IMPLICATIONS FOR PRACTICE: Healthcare providers should implement CE interventions during hospital care and recommend home-based CE interventions to patients who have barriers to performing hospital-based sessions.

Drug repurposing based on the similarity gene expression signatures to explore for potential indications of quercetin: a case study of multiple sclerosis.

Quercetin (QR) is a natural flavonol compound widely distributed in the plant kingdom with extensive pharmacological effects. To find the potential clinical indications of QR, 156 differentially expressed genes (DEGs) regulated by QR were obtained from the Gene Expression Omnibus database, and new potential pharmacological effects and clinical indications of QR were repurposed by integrating compounds with similar gene perturbation signatures and associated-disease signatures to QR based on the Connectivity Map and Coexpedia platforms. The results suggested QR has mainly potential therapeutic effects on multiple sclerosis (MS), osteoarthritis, type 2 diabetes mellitus, and acute leukemia. Then, MS was selected for subsequent animal experiments as a representative potential indication, and it found that QR significantly delays the onset time of classical MS model animal mice and ameliorates the inflammatory infiltration and demyelination in the central nervous system. Combined with network pharmacology technology, the therapeutic mechanism of QR on MS was further demonstrated to be related to the inhibition of the expression of inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-17A, and IL-2) related to TNF-α/TNFR1 signaling pathway. In conclusion, this study expanded the clinical indications of QR and preliminarily confirmed the therapeutic effect and potential mechanism of QR on MS.

Lateral Dorsal Basal Lung Resection Based on Functional Preserving Sublobectomy Method: Single-Center Experience.

PURPOSE: Functional preserving sublobectomy (FPSL), a novel balancing strategy for segmentectomy and wedge resection, allows rapid and accurate removal of invisible nodules without the use of any preoperative localization markers. This study aimed to share single-center experience of lateral dorsal basal lung resection based on FPSL, so as to provide new surgical options for thoracic surgeons. METHODS: A retrospective analysis was performed on 13 patients who underwent thoracoscopic basal lung resection after FPSL at XX hospital from January 2021 to August 2022. RESULTS: The operation was successfully performed in 13 patients by using FPSL, including 12 patients with malignant tumors. The mean operating time was 107.5 ± 25.6 min. The mean postoperative hospital stay was 3.7 ± 2.4 days. None of the patients needed extended excision, such as an entire basal or inferior lobectomy. CONCLUSION: Our single-center experience showed that the FPSL method only dealt with the target vessels, which greatly reduced the technical difficulty of surgery. In addition, both arteries and veins could be used as target vessels, and in particular cases such as undeveloped interlobar fissure, the operation could still be completed successfully. Lateral dorsal basal lung resection based on FPSL may be a new surgical option for surgeons.

The prognostic value of cancer stage-associated genes in clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is a highly prevalent subtype of malignant renal tumor, but unfortunately, the survival rate remains unsatisfactory. The aim of the present study is to explore genomic features that are correlated with cancer stage, allowing for the identification of subgroups of ccRCC patients with high risk of unfavorable outcomes and enabling prompt intervention and treatment. METHODS: We compared the gene expression levels across ccRCC patients with diverse cancer stages from The Cancer Genome Atlas (TCGA) database, which revealed characteristic genes associated with tumor stage. We then extracted prognostic genes and used least absolute shrinkage selection operator (LASSO) regression to select four genes for feature extraction and the construction of a prognostic risk model. RESULTS: We have identified a total of 171 differentially expressed genes (DEGs) that are closely linked to the tumor stage of ccRCC through difference analysis. A prognostic risk model constructed based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 holds significant prognostic value in ccRCC. The results of the functional enrichment analysis imply that the DEGs are mainly involved in the regulation of immune-related signaling pathways, and therefore may have a significant function in immune system regulation of ccRCC. CONCLUSIONS: Our study has successfully identified significant DEGs between high- and low-staging groups of ccRCC using bioinformatics methods. The construction of a prognostic risk model based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 has displayed promising prognostic significance, indicating its valuable potential for clinical application.

Stronger effects of simultaneous warming and precipitation increase than the individual factor on soil bacterial community composition and assembly processes in an alpine grassland.

Composition and traits of soil microbial communities that closely related to their ecological functions received extensive attention in the context of climate changes. We investigated the responses of soil bacterial community structure, traits, and functional genes to the individual warming, precipitation increases, and the combination of warming and precipitation increases in an alpine grassland in the Qinghai-Tibet Plateau that is experiencing warming and wetting climate change. Soil properties, plant diversity and biomass were measured, and the ecological processes and environmental factors driving bacterial community changes were further explored. Results indicated that the Shannon diversity of soil bacterial communities decreased significantly only under the combination treatment, which might due to the decreased plant diversity. Soil bacterial community composition was significantly correlated with soil pH, and was affected obviously by the combination treatment. At the taxonomic classification, the relative abundance of Xanthobacteraceae and Beijerinckiaceae increased 127.67 and 107.62%, while the relative abundance of Rubrobacteriaceae and Micromonosporaceae decreased 78.29 and 54.72% under the combination treatment. Functional genes related to nitrogen and phosphorus transformation were enhanced in the combination treatment. Furthermore, weighted mean ribosomal operon copy numbers that positively correlated with plant aboveground biomass increased remarkably in the combination treatment, indicating a trend of life-history strategies shift from oligotrophic to copiotrophic. Stochastic processes dominated soil bacterial community, and the proportion of stochasticity increased under the combination treatment. Our study highlights the significant effects of simultaneous warming and precipitation increase on soil bacterial community.

Establishing a quantitative assessment methodology framework of water conservation based on the water balance method under spatiotemporal and different discontinuous ecosystem scales.

Water conservation (WC) is an essential terrestrial ecosystem service that mitigates surface runoff and replenishes groundwater, which has received considerable attention under the dual pressures of climate change and human activity. However, there is insufficient understanding of the trends in WC changes on temporal (annual, monthly, daily), spatial, and ecosystem scales. This study proposed a quantitative assessment methodology framework (QAMF) for analyzing the spatiotemporal variation of WC under different discontinuous ecosystems. The QAMF mainly used models and methods such as the hydrological model (SWAT), calibration and uncertainty program (SWAT-CUP), WC calculation formula (water balance method), and spatial analysis method (empirical orthogonal function and wavelet analysis). It was applied to the source region of the Yellow River (SRYR), where the ecological landscape pattern underwent varying degrees of degradation, and WC capacity decreased. The results show that: Firstly, the constructed SWAT in the SRYR had high accuracy, and the proposed formula for calculating WC was suitable for multi-temporal scale analysis of WC in spatially distributed discontinuous basins. Secondly, the annual and monthly WC were respectively 81.00-184.13 mm and -28.58-107.64 mm, and daily WC was positive during extreme precipitation periods and negative during dry periods. The regulating effect of WC was fully reflected on the daily scale, partially reflected on the monthly scale, and absent on the annual scale. Third, the crucial WC area was mainly distributed in the southeast, and there was a significant primary yearly cycle of WC in the SRYR. Finally, different ecosystems exhibited different WC capabilities, and protecting the diversity of ecosystems played an essential role in maintaining and improving the WC function in the SRYR. This project has great scientific significance and technological support for scientifically evaluating the WC capacity in the SRYR.

Eltrombopag with or without Tacrolimus for relapsed/refractory acquired aplastic anaemia: a prospective randomized trial.

This trial compared eltrombopag (EPAG)+tacrolimus and EPAG monotherapy in patients with refractory/relapsed acquired aplastic anaemia (AA). Patients with refractory/relapsed AA were randomly assigned to receive either EPAG+tacrolimus or EPAG monotherapy at a ratio of 2:1. Patient response, safety, clonal evolution and survival were compared. In total, 114 patients were included in the analysis, with 76 patients receiving EPAG+tacrolimus and 38 receiving EPAG only. With a median follow-up of 18 (6-24) months, the overall response rate (ORR) for patients treated with EPAG+tacrolimus and EPAG alone was 38.2% vs. 31.6% (P = 0.490) at the 3rd month, 61.8% vs. 39.5% (P = 0.024) at the 6th month, 64.5% vs. 47.1% (P = 0.097) at the 12th month, and 60.5% vs. 34.2% (P = 0.008) at the last follow-up. The rate of each adverse event, overall survival curves (P = 0.635) and clonal evolution rate (P = 1.000) were comparable between the groups. A post hoc subgroup analysis showed that EPAG+tacrolimus could have advantage over EPAG monotherapy in terms of the ORR at the 6th month (P = 0.030)/last follow-up (P = 0.013) and the cumulative relapse-free survival (RFS) curves (P = 0.048) in patients <60 years old.

Predictive value for mortality of left ventricular wall thickness in dilated cardiomyopathy.

AIMS: The purpose of this study was to explore the predictive value of wall thickness measured by cardiac magnetic resonance (CMR) for all-cause mortality in dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: DCM patients who underwent CMR and completed the regular follow-up were included in this study. The left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic volume (LVEDV), left ventricular posterior wall thickness (PWT), interventricular septum thickness (IVST), left ventricular ejection fraction, and left ventricular mass (LVM) were measured by CMR. The presence and extent of late gadolinium enhancement (LGE) were also assessed. The relative posterior wall thickness (RWTPW ) and relative interventricular septum wall thickness (RWTIVS ) were defined by the following equations: RWTPW  = (2 × PWT)/LVDd, and RWTIVS  = (2 × IVST)/LVDd. All patients received regular telephone and outpatient follow-up. The primary endpoint was all-cause mortality. A total of 161 patients were enrolled in this study, including 126 (78.3%) males. The mean age was 52.3 ± 13.6 years. During the median follow-up of 47 months (interquartile range 32-57 months), 41 (24.8%) patients died. Compared with the non-death group, LVDd (75.2 ± 11.9 vs. 70.5 ± 8.8 mm; P = 0.025) was greater in the death group, while PWT [5.2 mm (3.7-6.8) vs. 6.9 mm (5.3-8.6); P < 0.001], IVST [8.2 mm (6.5-9.5) vs. 9.3 mm (7.4-10.5); P = 0.005], RWTPW [0.15 (0.11-0.19) vs. 0.20 (0.15-0.25); P < 0.001], RWTIVS [0.22 (0.17-0.26) vs. 0.26 (0.22-0.31); P < 0.001], and LVM/LVEDV ratio (0.5 ± 0.2 vs. 0.7 ± 0.2 g/mL; P < 0.001) were lower. The presence of LGE [LGE(+)] was more frequent in the death group (75.6% vs. 58.3%; P = 0.048). However, the LGE extent was not significantly different between the two groups [4 (1-7) vs. 2 (0-6); P = 0.096]. Multivariate Cox regression analysis showed that PWT [hazard ratio (HR) 0.086, 95% confidence interval (CI) 0.665-0.976; P < 0.05] and RWTPW (HR 0.001, 95% CI 0.000-0.502; P < 0.05) were independent predictors of all-cause death. In contrast, IVST, RWTIVS , and the presence of LGE were not clearly associated with death. CONCLUSIONS: PWT measured by CMR is an independent predictor of all-cause mortality in DCM patients. However, there was no significant correlation between septum wall thickness and mortality.

Circular RNA in cholangiocarcinoma: A systematic review and bibliometric analysis.

BACKGROUND: Cholangiocarcinoma (CCA) is a common primary liver malignancy with a poor prognosis. Many studies have demonstrated the involvement of circular RNAs (circRNAs) in tumorigenesis and progression. METHODS: Four online databases (PubMed, Web of Science, Embase, and Scopus) were searched on May 04, 2023, for original papers regarding CCA and circRNAs. Bibliometric analysis of included studies was performed on R Studio and GraphPad Prism. RESULTS: Thirty studies were included in the systematic review and bibliometric analysis. The systematic review showed that circRNAs were involved in CCA proliferation, invasion, metastasis, chemotherapy resistance, and other biological processes and were related to the prognosis of patients and many clinicopathological features. Exosomal circRNAs provide a new idea for the early diagnosis of CCA. The bibliometric analysis showed a significant upward trend in the number of studies on CCA and circRNAs. The 30 included papers had 201 authors and were published in 22 English journals. The first paper was published in 2018, and the second paper was the most cited (148 citations). CONCLUSION: This systematic review and bibliometric analysis demonstrates that circRNAs in CCA have not been studied enough. CircRNAs play an important role in the occurrence and progression of CCA. They may become new targets for the diagnosis, treatment, and prognostic monitoring of CCA.