Prior-guided individualized thalamic parcellation based on local diffusion characteristics.

Comprising numerous subnuclei, the thalamus intricately interconnects the cortex and subcortex, orchestrating various facets of brain functions. Extracting personalized parcellation patterns for these subnuclei is crucial, as different thalamic nuclei play varying roles in cognition and serve as therapeutic targets for neuromodulation. However, accurately delineating the thalamic nuclei boundary at the individual level is challenging due to intersubject variability. In this study, we proposed a prior-guided parcellation (PG-par) method to achieve robust individualized thalamic parcellation based on a central-boundary prior. We first constructed probabilistic atlas of thalamic nuclei using high-quality diffusion MRI datasets based on the local diffusion characteristics. Subsequently, high-probability voxels in the probabilistic atlas were utilized as prior guidance to train unique multiple classification models for each subject based on a multilayer perceptron. Finally, we employed the trained model to predict the parcellation labels for thalamic voxels and construct individualized thalamic parcellation. Through a test-retest assessment, the proposed prior-guided individualized thalamic parcellation exhibited excellent reproducibility and the capacity to detect individual variability. Compared with group atlas registration and individual clustering parcellation, the proposed PG-par demonstrated superior parcellation performance under different scanning protocols and clinic settings. Furthermore, the prior-guided individualized parcellation exhibited better correspondence with the histological staining atlas. The proposed prior-guided individualized thalamic parcellation method contributes to the personalized modeling of brain parcellation.

First complete mitogenome of Massarineae and its contribution to phylogenetic implications in Pleosporales.

Endophytic fungi play an important role in the growth and development of traditional Chinese medicine plants. We isolated a strain of Acrocalymma vagum from the endophytic fungi of the traditional Chinese plants Paris. To accurately identify this endophytic fungal species of interest, we sequenced the mitochondrial genome of A. vagum, which is the first discovered mitochondrial genome in Massarineae. The A. vagum mitochondrial genome consists of a 35,079-bp closed circular DNA molecule containing 36 genes. Then, we compared the general sequence characteristics of A. vagum with those of Pleosporales, and the second structure of the 22 tRNAs was predicted. The phylogenetic relationship of A. vagum was constructed using two different data sets (protein-coding genes and amino acids). The phylogenetic tree shows that A. vagum is located at the root of Pleosporales. The analysis of introns shows that the number of introns increases with the increase in branch length. The results showed that monophyly was confirmed for all families in Pleosporales except for Pleosporaceae. A. vagum is an ancient species in the Pleosporales, and Pleosporaceae may require further revision. In Pleosporales, the number of introns is positively correlated with branch length, providing data for further study on the origin of introns.

Clinical Study on the Management of Aortic Dissection Involving the Aortic Arch through Endovascular Isolation and In Situ Fenestration with Covered Stent.

Objective: This study aimed to investigate the clinical effectiveness of the SilverFlow branch stent through endovascular isolation and in situ fenestration (ISF) for the treatment of aortic dissection (AD) involving the aortic arch. Methods: A total of 21 patients with AD involving the aortic arch, admitted to our hospital between September 2021 and January 2023, were selected for this prospective study. All patients underwent treatment with an endoluminal isolated ISF-covered stent, with the branch stent being the SilverFlow, developed by Shenzhen Xianjian Company. We assessed the success rate of the ISF procedure stent-related complications and compared the volumes of the true and false cavities before and after treatment. Follow-up evaluations were conducted 1, 3, and 6 months post-operation, focusing on neurological complications, mortality, and the need for secondary interventional treatment. Results: Among the 21 AD patients with aortic arch involvement, 20 (95.23%) underwent non-emergency surgery, while 1 (4.76%) required emergency surgery due to cardiac ischemia and signs of dissection rupture. All surgeries were successfully completed. After treatment, the average volume of the true lumen significantly decreased compared to pre-treatment levels, while the volume of the false lumen significantly increased (P < .05). The success rate was 100%, with only one case (4.76%) experiencing type I internal leakage. There were no cases of stent displacement, distortion, or fenestration vessel occlusion. One patient (4.76%) succumbed to acute pericardial tamponade, resulting in a mortality rate of 4.76%. Another patient (4.76%) suffered from upper limb ischemia, significantly improving with antithrombotic drug treatment. No occurrences of stroke, visceral ischemia, or other complications were reported, and no secondary interventional treatments were required. Conclusions: The application of the SilverFlow branch stent for endovascular isolation of ISF in AD cases involving the aortic arch demonstrates a high success rate, low complication and mortality rates, and significant clinical feasibility and value.

Efficacy and safety of Chinese patent medicine Xiao Yao San in polycystic ovary syndrome: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age worldwide. Previous studies using randomized controlled trials (RCTs) have revealed that Xiao Yao San (XYS), a classic Chinese patent medicine formula, can effectively treat PCOS. However, the entire evidence has yet to be systematically summarized. AIM OF THE STUDY: The aim of this systematic review and meta-analysis of clinical trials was to assess the effect of XYS for the treatment of PCOS. MATERIALS AND METHODS: 7 databases were thoroughly reviewed for RCTs published from inception to July 2022, assessing the effect of XYS in treating PCOS, including Cochrane Library, PubMed, Embase, Wan Fang Database, Chinese Biomedical Database, China National Knowledge Infrastructure, and China Science and Technology Journal Database. Outcome measures included ovulation rate, pregnancy rate, hormonal levels, and glycemic parameters. Either a random-effects model or a fixed-effect models was used to pool data. Pooled effect sizes were reported as odds ratios (ORs) or standardized mean differences (SMDs) with their 95% confidence intervals (CIs). RESULTS: A total of 9 trials including 736 PCOS patients met the selection criteria. Our results indicate that XYS plus conventional medicines for PCOS significantly improved ovulation rate (OR = 2.45, 95% CI = 1.94 to 3.08, P < 0.001) and pregnancy rate (OR = 2.65, 95% CI = 1.87 to 3.75, P < 0.001), meanwhile decreased levels of fasting insulin (FINS) (SMD = - 0.46, 95% CI: 0.65 to - 0.27, P < 0.001) and homeostatic model assessment for insulin resistance (HOMA-IR) (SMD = - 0.65, 95% CI = - 0.93 to - 0.37, P < 0.001). XYS plus conventional medicines for PCOS did not have a significant impact on levels of total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and fasting plasma glucose (FPG). No serious adverse reactions were observed. CONCLUSION: XYS combined with conventional medicines can improve ovulation and pregnancy rates, decrease FINS and HOMA-IR in PCOS patients, indicating that XYS treatment may be used as a promising adjuvant therapy to the conventional medicines of PCOS. However, due to significant heterogeneity and methodological shortcomings, these results should be interpreted with great caution. Larger, higher quality RCTs are needed to rigorously assess the effect of XYS as a complementary therapy in managing PCOS.

Ginsenoside Rg1 Reduces Oxidative Stress Via Nrf2 Activation to Regulate Age-Related Mesenchymal Stem Cells Fate Switch Between Osteoblasts and Adipocytes.

Background: An important feature of aging cells is the gradual loss of physiological integrity. As aging progresses, MSCs change preferring to differentiate toward adipocytes rather than osteoblasts. Oxidative stress accumulation is an important factor in age-related bone loss. Many experiments have demonstrated the good therapeutic effect of Ginsenoside (Rg1) on oxidative stress injury. In this study, we investigated the effect of Rg1 on the osteogenic-adipogenic differentiation balance of bone marrow mesenchymal stem cells (BMMSC). Objective: To analyze the potential application value of Rg1 in the treatment of senile osteoporosis. Methods: BMMSCs were isolated from healthy donors of different ages and identified based on isotype and by multi-differentiation induction. Rg1 was used to treat BMMSCs, The differentiation propensity was analyzed by induction of differentiation assay. Antioxidant capacity of BMMSCs as measured by oxidative stress product assay Related mechanism studies were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunofluorescence, western blotting, and inhibitor treatment. Moreover, Observation of the effects of Rg1 on aging BMMSCs under in vivo conditions by treatment of aged mice with Rg1 injections. Results: Rg1 treatment rescued age-induced switch of BMMSCs differentiation fate in vitro. In elderly people, Rg1 markedly increased osteogenic differentiation of BMMSCs by decreasing oxidative stress, while inhibiting adipogenic differentiation. However, this effect was abolished in BMMSCs by an Nrf2-inhibitor. Notably, aging mice showed a reduction in adipocyte distribution in the bone marrow and a decrease in oxidative stress products after a 3-month period of Rg1 treatment. Conclusion: We have uncovered a novel function for Rg1 that involves attenuating bone loss via Nrf2 antioxidant signaling, which in turn may potentially be utilized as a therapeutic agent for improving osteogenic differentiation in aging BMMSCs.

Revealing the Therapeutic Targets and Mechanism of Ginsenoside Rg1 for Liver Damage Related to Anti-Oxidative Stress Using Proteomic Analysis.

Ginsenoside Rg1 is an important active substance isolated from the root of ginseng. In previous studies, Rg1 has shown excellent therapeutic effects in antioxidant, anti-inflammatory, and metabolic modulation. However, the therapeutic targets of Rg1 are still unknown. In this study, we investigated the therapeutic effects of Rg1 on oxidative stress-related liver damage. The oxidative stress damage model was achieved by intraperitoneal injection of D-galactose (D-gal) for 42 consecutive days in C57BL/6J mice. Rg1 treatment started on Day 16. Body weight, liver weight, degree of hepatic oxidative stress damage, serum lipid levels, and hepatic lipid and glucose metabolism were measured. Proteomics analysis was used to measure liver protein expression. The differential expression proteins were analyzed with bioinformatics. The results showed that Rg1 treatment attenuated liver damage from oxidative stress, reduced hepatic fat accumulation, promoted hepatic glycogen synthesis, and attenuated peripheral blood low-density lipoprotein (LDL), cholesterol (CHO), and triglycerides (TG) levels. Proteomic analysis suggested that Rg1 may regulate hepatocyte metabolism through ECM-Receptor, the PI3K-AKT pathway. The epidermal growth factor receptor (EGFR) and activator of transcription 1 (STAT1) may be the key protein. In conclusion, this study provides an experimental basis for further clarifying the specific mechanism of Rg1 in the treatment of oxidative stress damage-related liver disease.

Injectable hyaluronan/MnO2 nanocomposite hydrogel constructed by metal-hydrazide coordinated crosslink mineralization for relieving tumor hypoxia and combined phototherapy.

Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO2 nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn2+ and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous H2O2 into O2 but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O2-enhanced efficient topical dual-phototherapy of breast cancer.

Antibacterial Activity and Components of the Methanol-Phase Extract from Rhizomes of Pharmacophagous Plant Alpinia officinarum Hance.

The rhizomes of Alpinia officinarum Hance (known as the smaller galangal) have been used as a traditional medicine for over 1000 years. Nevertheless, little research is available on the bacteriostatic activity of the herb rhizomes. In this study, we employed, for the first time, a chloroform and methanol extraction method to investigate the antibacterial activity and components of the rhizomes of A. officinarum Hance. The results showed that the growth of five species of pathogenic bacteria was significantly inhibited by the galangal methanol-phase extract (GMPE) (p < 0.05). The GMPE treatment changed the bacterial cell surface hydrophobicity, membrane fluidity and/or permeability. Comparative transcriptomic analyses revealed approximately eleven and ten significantly altered metabolic pathways in representative Gram-positive Staphylococcus aureus and Gram-negative Enterobacter sakazakii pathogens, respectively (p < 0.05), demonstrating different antibacterial action modes. The GMPE was separated further using a preparative high-performance liquid chromatography (Prep-HPLC) technique, and approximately 46 and 45 different compounds in two major component fractions (Fractions 1 and 4, respectively) were identified using ultra-HPLC combined with mass spectrometry (UHPLC-MS) techniques. o-Methoxy cinnamaldehyde (40.12%) and p-octopamine (62.64%) were the most abundant compounds in Fractions 1 and 4, respectively. The results of this study provide data for developing natural products from galangal rhizomes against common pathogenic bacteria.

Genome-wide CRISPR Screening Reveals Pyrimidine Metabolic Reprogramming in 5-FU Chronochemotherapy of Colorectal Cancer.

Objective: Disruption of the circadian rhythm is associated with cancer occurrence, response to chemotherapy, and poor prognosis. Thus, using internal clock-based chronotherapy to optimize the administration time may improve the therapeutic effects of anticancer drugs while reducing the side effects. Chronotherapy with 5-fluorouracil (5-FU) has been observed in colorectal cancer (CRC) for a long time, but its effect is under controversial and the mechanism remains unclear. Methods: Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening and RNA-sequencing were combined to identify the potential genes or pathways involved in 5-FU chronochemotherapy. Genetic deletion or overexpression of pyrimidine metabolic pathway genes were conducted to examine cellular viability with or without 5-FU via flow cytometry. Western blotting, qPCR, chromatin immunoprecipitation, gain-of-function and loss-of-function assays of several CRC cell lines in vitro and in vivo were used to elaborate and validate the mechanism of 5-FU chronotherapeutic effects. Results: Chronochemotherapeutic effects of 5-FU on CRC in vivo were verified. Furthermore, 5-FU chronochemotherapy related genes such as UPP2, UCK2 and UMPS in the pyrimidine metabolic pathway were identified. Disturbance in these genes, especially UMPS, perturbs 5-FU treatment outcomes in CRC cells. Mechanistically, the core circadian gene, brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), extensively regulate gene expression in pyrimidine metabolic pathway by binding to E-box element in the promoter region of key genes such as UMPS and perturb their enzymatic activities, thereby maintain diurnal efficacy of 5-FU in CRC cells. Conclusion: This study uncovered a new mechanism by which a core circadian gene BMAL1 increases the effectiveness of 5-FU by enhancing the expression and enzymatic activities of key genes in the pyrimidine metabolic pathway in CRC cells. The findings suggest a novel strategy for CRC chemotherapy by targeting chrono-modulated genes of the 5-FU metabolic pathway.

Effects of Milk Replacer-Based Lactobacillus on Growth and Gut Development of Yaks' Calves: a Gut Microbiome and Metabolic Study.

The gut microbiota and its metabolic activities are crucial for maintaining host homoeostasis and health, of which the role of probiotics has indeed been emphasized. The current study delves into the performance of probiotics as a beneficial managemental strategy, which further highlights their impact on growth performance, serologic investigation, gut microbiota, and metabolic profiling in yaks' calves. A field experiment was employed consisting of 2 by 3 factorial controls, including two development stages, namely, 21 and 42 days (about one and a half month), with three different feeding treatments. Results showed a positive impact of probiotic supplements on growth performance by approximately 3.16 kg (P < 0.01) compared with the blank control. Moreover, they had the potential to improve serum antioxidants and biochemical properties. We found that microorganisms that threaten health were enriched in the gut of the blank control with the depletion of beneficial bacteria, although all yaks were healthy. Additionally, the gut was colonized by a microbial succession that assembled into a more mature microbiome, driven by the probiotics strategy. The gut metabolic profiling was also changed significantly after the probiotic strategy, i.e., the concentrations of metabolites and the metabolic pattern, including enrichments in protein digestion and absorption, vitamin digestion and absorption, and biosynthesis of secondary metabolites. In summary, probiotics promoted gut microbiota/metabolites, developing precise interventions and achieving physiological benefits based on intestinal microecology. Hence, it is important to understand probiotic dietary changes to the gut microbiome, metabolome, and the host phenotype. IMPORTANCE The host microbiome is a composite of the trillion microorganisms colonizing host bodies. It can be impacted by various factors, including diet, environmental conditions, and physical activities. The yaks' calves have a pre-existing imbalance in the intestinal microbiota with an inadequate feeding strategy, resulting in poor growth performance, diarrhea, and other intestinal diseases. Hence, targeting gut microbiota might provide a new effective feeding strategy for enhancing performance and maintaining a healthy intestinal environment. Based on the current findings, milk replacer-based Lactobacillus feeding may improve growth performance and health in yaks' calves.

Rg1 Protects Hematopoietic Stem Cells from LiCl-Induced Oxidative Stress via Wnt Signaling Pathway.

Background: Ginsenoside Rg1 is a major component of ginseng with antioxidative and antiaging effects, which is a traditional Chinese medicine. In this study, we investigated the potential spillover and mechanism of action of Rg1 on LiCl-driven hematopoietic stem cell aging. Results: Collect the purified Sca-1+ hematopoietic cells for differentiation ability detection and biochemical and molecular labeling. The experiment found that Rg1 plays an antiaging role in reversing the SA-ß-gal staining associated with LiCl-induced hematopoietic stem cell senescence, the increase in p53 and p21 proteins, and sustained DNA damage. At the same time, Rg1 protects hematopoietic cells from the reduced differentiation ability caused by LiCl. In addition, Rg1 increased the excessive inhibition of intracellular GSK-3ß protein, resulting in the maintenance of ß-catenin protein levels in hematopoietic cells after LiCl treatment. Then, the target gene level of ß-catenin can be maintained. Conclusions: Rg1 exerts the pharmacological effect of maintaining the activity of GSK-3ß in Sca-1+ hematopoietic cells, enhances the antioxidant potential of cells, improves the redox homeostasis, and thus protects cells from the decline in differentiation ability caused by aging. This study provides a potential therapeutic strategy to reduce stem cell pool failure caused by chronic oxidative damage to hematopoietic stem cells.

Mutyh deficiency downregulates mitochondrial fusion proteins and causes cardiac dysfunction via α-ketoglutaric acid reduction with oxidative stress.

MutY homolog (MUTYH), an important protein in base excision repair (BER) system, excises adenine in the nascent strand opposite 8-oxoguanine in template DNA and restores G:C base-pair to maintain the fidelity of DNA replication. The loss of MUTYH causes oxidative stress and influences cardiac function, but the mechanism remains to be addressed. Here we demonstrate that Mutyh deficiency alters mitochondrial structure and impairs mitochondrial function through downregulation of mitochondrial fusion protein Mfn2 and alteration of the ratio of L-Opa1/S-Opa1 accompanied by reduction of α-ketoglutaric acid (α-KG) under oxidative stress condition. Further analysis reveals that the Mutyh deficiency may cause downregulation of histone demethylases and DNA demethylases and inhibition of the Mfn2 transcription. Oxidative stress associated with tert-butyl hydroperoxide (t-BHP) exposure results in the degradation of L-Opa1 and impairs the balance of L-Opa1/S-Opa1. Interestingly, α-KG supplementation alleviates the damage associated with Mutyh deficiency, restores the expression of Mfn2 and prevents degradation of L-Opa1. The current study demonstrates the relationship among Mutyh deficiency-coupled oxidative stress, the altered expressions of Mfn2 and Opa1, and the mitochondrial dysfunction, in which an intermediate in the tricarboxylic acid (TCA) cycle, α-KG has a key regulatory role.

Genome-wide identification, structural and gene expression analysis of the nitrate transporters (NRTs) family in potato (Solanum tuberosum L.).

Nitrogen (N2) is the most important source of mineral N for plant growth, which was mainly transported by nitrate transporters (NRTs). However, little is known about the NRT gene family in potato. In this study, StNRT gene family members were identified in potato. In addition, we performed StNRT subfamily classification, gene structure and distribution analysis, and conserved domain prediction using various bioinformatics tools. Totally, 39 StNRT gene members were identified in potato genome, including 33, 4 and 2 member belong to NRT1, NRT2, and NRT3, respectively. These 39 StNRT genes were randomly distributed on all chromosomes. The collinearity results show that StNRT members in potato are closely related to Solanum lycopersicum and Solanum melongena. For the expression, different members of StNRT play different roles in leaves and roots. Especially under sufficient nitrogen conditions, different members have a clear distribution in different tissues. These results provide valuable information for identifying the members of the StNRT family in potato and could provide functional characterization of StNRT genes in further research.

Milk replacer supplementation in early life optimizes the development of intestinal microbes in goats.

Colonization and development of the gut microbiome during early life is important in establishing a host-microbial symbiotic relationship. It contributes to maintaining health and well-being throughout the life span. To date, early longitudinal development of intestinal microflora in the ileum micro-ecology of the Yimeng black goats (YBGs) is rare. The purpose of this research was to study the effect of milk replacer with age on the ileal microbiota growth and maturation in YBGs throughout the post-weaning phase. The newborn YBGs (n = 24) were divided into two groups, i.e., milk replacer (R group) and control group (B group). The microbiome of Ileum was observed on days 15, 25, 45, and 75. When compared with baseline (B group), the R group's alpha diversity was lower (day 15, 25, 45), but it gradually approached and exceeded the baseline in the later stages (day 75). On the time axis, the richness of intestinal microflora was increased with age, but there was no statistically significant difference. The relative abundances of Proteobacteria, Firmicutes, Peptoclustridium, Lachnospiraceae, and Prevotellaceae showed a continuous trend of increase initially. They then decreased except Ruminococcaceae, which reflected the gradual maturity of intestinal microbial development. Milk replacer treatment temporarily increased the abundance of Actinomycetes (day 25 and 45), while the relative proportion of several intestinal bacteria such as Parasutterella, Megasphaera, Prevotellaceae, Akkermansia, and Subdoligranulum species were significantly higher in R group than in B group. The major changes in gut microflora composition might reflect positive effect of milk replacer on the development and maturation of the intestine during the early stage, connecting with substrate availability in the gut. Our study provides an effective strategy to promote the development of the gut microbiome, which is helpful for a smooth transition during the early-weaning period in YBGs.

Application of traditional Chinese and Western medicine combined with chronic disease management in pulmonary rehabilitation and evaluation of efficacy.

OBJECTIVE: This study evaluated the efficacy of traditional Chinese and western medicine combined with chronic disease management on rehabilitation of chronic obstructive pulmonary disease (COPD) patients. METHODS: A total of 199 COPD patients in Shanghai Construction Group (SCG) Hospital were recruited as research objects. The control group (CG) consisted of 100 patients treated with conventional western chronic disease management, and the research group (RG) consisted of 99 patients treated with chronic disease management with combined traditional Chinese and western medicine. The efficacy, pulmonary rehabilitation performance, compliance score, 6-minute walk test (6MWT), modified Medical Research Council dyspnoea scale (MMRC), COPD assessment test (CAT), pulmonary function (PaO2, PaCO2, FEV1, PEF), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and patient satisfaction between the two groups were compared. RESULTS: Pulmonary rehabilitation performance, 6MWT results, and patient satisfaction in the RG were significantly better than those in the CG. The total effective rate, compliance score, PaO2, FEV1 and PEF of the RG were significantly higher than those of the CG. After treatment, the COPD symptom score, CAT score, PaCO2, SAS score and SDS score in the RG were significantly lower than those in the CG. CONCLUSION: Chronic disease management with combined traditional Chinese and western medicine has great application value and high efficacy in pulmonary rehabilitation.

A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE's anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

Effects of Harvest Time on the Yield, Quality and Active Substance of Torreya grandis Nut and Its Oil.

Torreya grandis is an important economic tree species in China. It provides nutritional value and is important to the health care industry. There are ongoing issues with product quality which are primarily related to improper management and early harvest. This study was carried out during the fruit ripening processes to evaluate the influence of harvesting date on T. grandis quality, and to determine the optimal harvest period. The effects of harvest time on the variation of quality and nutritional parameters of T. grandis nuts and its oil were evaluated, and the optimal harvest period was determined. The results showed that harvest timing had a strong effect on both oil yield and quality. Prolonged ripening could induce higher levels of kernel rate, fruit inclusions, oil and nutritional quality. When the sample harvested in the mid-September, the kernel rate and oil content were increased by 1.88±0.31% and 6.65±0.47%, respectively, compared to samples harvested in the beginning of late-August. Similarly, the mid-September harvest resulted in total unsaturated fatty acids content of the oil being increased by 5.3±0.34%, the FFA and peroxide value being decreased by 40.7±0.15% and 76±0.08%, respectively, and total tocopherols and free amino acids were increased 7.5±0.24% and 47.3±0.15%, respectively, compared to the samples harvested on Aug. 25. The results indicated that the optimal harvest time of T. grandis fruits was mid-September as it was beneficial for improving the quality of T. grandis nut and its oil. It was suggested that T. grandis fruit should be harvested later.

Efficacy and safety of Si-Jun-Zi-Tang-based therapies for functional (non-ulcer) dyspepsia: a meta-analysis of randomized controlled trials.

BACKGROUND: The traditional Chinese medicine formula Si-Jun-Zi-Tang (SJZT) has a long history of application in the treatment of functional dyspepsia (non-ulcer dyspepsia, FD)-like symptoms. SJZT-based therapies have been claimed to be beneficial in managing FD. This study aimed to assess the efficacy and safety of SJZT-based therapies in treating FD by meta-analysis. METHODS: Systematic searches for RCTs were conducted in seven databases (up to February 2019) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcome was response rate and the secondary outcomes were gastric emptying, quality of life, adverse effects and relapse rate. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias. RESULTS: A total of 341 potentially relevant publications were identified, and 12 RCTs were eligible for inclusion. For the response rate, there was a statically significant benefit in favor of SJZT-based therapies (RR = 1.23; 95% CI 1.17 to 1.30). However, the benefit was limited to modified SJZT (MSJZT). The relapse rate of FD patients received SJZT-based therapies was lower than that of patients who received conventional medicines (OR = 0.23; 95% CI 0.10 to 0.51). No SJZT-based therapies-related adverse effect was reported. CONCLUSION: SJZT-based prescriptions may be effective in treating FD and no serious side-effects were identified, but the effect on response rate appeared to be limited to MSJZT. The results should be interpreted with caution as all the included studies were considered at a high risk of bias. Standardized, large-scale and strictly designed RCTs are needed to further validate the benefits of SJZT-based therapies for FD management. TRIAL REGISTRATION: Systematic review registration: [PROSPERO registration: CRD42019139136 ].