Theoretical framework, indicator system and practical application of key biodiversity areas.

With the continuous decline of global biodiversity, biodiversity conservation has attracted more and more attention from the international society. In order to slow down the trend of biodiversity decline, it is particularly important to identify key areas for biodiversity conservation. However, most of current methods for identifying important areas have different assessment criteria and focus on different biological assemblages (species or communities) and ecosystem types. Key biodiversity areas (KBAs) are sites that contribute significantly to global biodiversity persistence. Unlike traditional research and identification methods, KBAs identification is based on a unified global standard to explore habitats that are critical to endangered plants and animals in terrestrial, freshwater, and marine ecosystems. Based on the theoretical and technical framework of KBAs, we summarized the system of identification criteria and assessment parameters for KBAs. The five high-level criteria are separated into eleven sub-level criteria. Among the eleven evaluation parameters, there is one evaluation parameter for the ecosystem level, eight evaluation parameters for the species level, one evaluation parameter for the gene level, and one comprehensive evaluation parameter. In addition, we analyzed the application of KBAs identification in biodiversity research and conservation combined with relevant domestic and foreign research cases. Furthermore, we discussed the future development direction and application prospect of KBAs identification method in China. This method could provide a new perspective for the formulation of ecological protection policies and the planning of naturally protected areas in China.

The complete chloroplast genome of Eastern Asian fern Bolbitis laxireticulata (Dryopteridaceae).

Bolbitis laxireticulata is a potential ornamental plant, which is restricted to eastern Asia. Here, we sequenced the complete chloroplast (cp) genome of B. laxireticulata and constructed a phylogenetic cp tree of Dryopteridaceae to study their relationships. The cp genome of B. laxireticulata is 153,093 bp in length, being made up of large single-copy (LSC, 83,169 bp), small single-copy (SSC, 21,538 bp), and a pair of region inverted repeats (IRs, 24,193 bp). It has 124 genes including 83 protein-coding genes, 33 tRNA genes, and eight rRNA genes. With the maximum-likelihood tree indicating, B. laxireticulata is more closely related to B. subcordata.

Cytokines/chemokines and immune checkpoint molecules in anti-leucine-rich glioma-inactivated 1 encephalitis.

OBJECTIVE: We aimed to investigate levels of cytokines/chemokines and immune checkpoint molecules in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. METHODS: The study recruited 12 patients with anti-LGI1 encephalitis and six non-inflammatory controls from the Qilu Hospital of Shandong University treated between January 2019 and December 2020. Serum levels of 30 cytokines/chemokines and 10 checkpoint molecules were measured in participants of both the groups. RESULTS: In contrast to those in the control group, 24 cytokines/chemokines and 5 immune checkpoint molecules were differentially expressed in patients with anti-LGI1 encephalitis, with 14 cytokines being upregulated and 10 being downregulated. There were 1033 enriched biological processes and 61 enriched Kyoto Encyclopedia of Genes and Genomes signaling pathways. CONCLUSION: A wide range of cytokines/chemokines and immune checkpoint molecules are implicated in immune regulation in anti-LGI1 encephalitis, indicating that they may serve as important targets in the development and treatment of the disease.

Phylogeny, character evolution, and biogeography of the fern genus Bolbitis (Dryopteridaceae).

Bolbitis is a pantropical fern genus of Dryopteridaceae with ca. 80 species mainly in tropical Asia. Earlier studies confirmed the monophyly of Bolbitis when Mickelia is excluded and identified three major clades in Bolbitis. However, earlier studies are based on relatively small sampling and the majority of Asian species are not sampled. In this study, DNA sequences of three plastid markers of 169 accessions representing ca. 68 (85 % of total) species of Bolbitis in nine out of the 10 series recognized by Hennipman (1977), and 54 accessions representing the five remaining bolbitidoid genera are used to infer a global phylogeny with a focus on Asian species. The major results include: (1) Bolbitis is strongly supported as monophyletic; (2) species of Bolbitis are resolved into four major clades and their relationships are: the Malagasy/Mascarene clade is sister to the rest, followed by the African clade which is sister to the American clade + the Asian clade; (3) six well-supported subclades are identified in the most speciose Asian clade; (4) the free-veined Egenolfia is embedded in Bolbitis and is paraphyletic in relation to species with anastomosing venation; (5) three series sensu Hennipman (1977), B. ser. Alienae, B. ser. Egenolfianae, and B. ser. Heteroclitae, are paraphyletic or polyphyletic; (6) evolution of six morphological characters is analyzed and free venation is found to have evolved from anastomosing venation and reversed to free venation in Bolbitis; and (7) biogeographical implications are drawn and it is shown that a single recent dispersal from Asia resulted in continental disjunction of closely related ferns of Bolbitis between Africa and America.

Increased formation of neutrophil extracellular traps in patients with anti-N-methyl-d-aspartate receptor encephalitis.

Background: Neutrophil extracellular traps (NETs) have been found to play an important role in several nervous system diseases. However, their role in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis remains unclear. The purpose of this study was to examine the possible role of NETs in anti-NMDAR encephalitis. Materials and methods: Eleven patients with anti-NMDAR encephalitis and ten healthy participants were enrolled. Plasma NETs levels were detected using an immunofluorescence assay and enzyme-linked immunosorbent assay. Additionally, we examined 10 plasma cytokines in patients with anti-NMDAR encephalitis and analyzed the correlation between citrullinated histone 3 levels and cytokine release. Results: Peripheral blood neutrophils from patients with anti-NMDAR encephalitis were more susceptible to NET generation. When compared with controls, cases of anti-NMDAR encephalitis showed elevated levels of IL-1 α, IL-6, IL-8, IL-13, MCP-1, and TNF-α (p < 0.05). Moreover, IL-6, IL-8, and TNF-α levels were positively correlated with H3Cit levels. Conclusion: We provide evidence that NETs may play a role in anti-NMDAR encephalitis, providing clues for elucidation of the pathogenesis of this disease.

Coexistence of multiple anti-neuronal antibodies in autoimmune encephalitis in China: A multi-center study.

Background: Given that the combination of multiple antibodies in autoimmune encephalitis (AE) is rare and its clinical significance is unclear, this study aimed to investigate the clinical characteristics and significance of overlapping multiple anti-neuronal antibodies in patients with AE. Methods: We conducted a retrospective analysis of the clinical characteristics, treatment, and prognostic details of 22 patients with multiple coexisting antibodies from multiple clinical centers in China. Results: Among the 276 patients who were AE antibody-positive, 22 (7.97%) had two or more antibodies. Among the 22 patients with coexisting AE-related antibodies, 14 patients (63.63%) were combined of cell surface and intracellular antibody, and the remaining 8 patients (36.36%) were detected to be cell surface antibody positive only. The main symptoms of the 22 patients in this cohort included fever, seizures, memory impairment, cognitive decline, and sleep disorders. Five (22.73%) patients had tumors, among whom four had small-cell lung cancers, and one had mediastinal tumors. A total of 20 patients were treated with steroids and intravenous immunoglobulin, and 18 showed varying degrees of symptomatic improvement after first-line immunotherapy. Three patients died of tumor progression or chemotherapy complications. Conclusion: The coexistence of multiple anti-neuronal antibodies in patients with AE may cause a superimposition and diversification of clinical manifestations. Combined paraneoplastic antibody positivity may be suggestive of an underlying malignancy.

Transcriptomic and Metabolomic Analyses Provide Insights into the Formation of the Peach-like Aroma of Fragaria nilgerrensis Schlecht. Fruits.

Fragaria nilgerrensis Schlecht. is a wild diploid strawberry species. The intense peach-like aroma of its fruits makes F. nilgerrensis an excellent resource for strawberry breeding programs aimed at enhancing flavors. However, the formation of the peach-like aroma of strawberry fruits has not been comprehensively characterized. In this study, fruit metabolome and transcriptome datasets for F. nilgerrensis (HA; peach-like aroma) and its interspecific hybrids PA (peach-like aroma) and NA (no peach-like aroma; control) were compared. In total, 150 differentially accumulated metabolites were detected. The K-means analysis revealed that esters/lactones, including acetic acid, octyl ester, δ-octalactone, and δ-decalactone, were more abundant in HA and PA than in NA. These metabolites may be important for the formation of the peach-like aroma of F. nilgerrensis fruits. The significantly enriched gene ontology terms assigned to the differentially expressed genes (DEGs) were fatty acid metabolic process and fatty acid biosynthetic process. Twenty-seven DEGs were predicted to be associated with ester and lactone biosynthesis, including AAT, LOX, AOS, FAD, AIM1, EH, FAH, ADH, and cytochrome P450 subfamily genes. Thirty-five transcription factor genes were predicted to be associated with aroma formation, including bHLH, MYB, bZIP, NAC, AP2, GATA, and TCPfamily members. Moreover, we identified differentially expressed FAD, AOS, and cytochrome P450 family genes and NAC, MYB, and AP2 transcription factor genes that were correlated with δ-octalactone and δ-decalactone. These findings provide key insights into the formation of the peach-like aroma of F. nilgerrensis fruits, with implications for the increased use of wild strawberry resources.

Genome size evolution of the extant lycophytes and ferns.

Ferns and lycophytes have remarkably large genomes. However, little is known about how their genome size evolved in fern lineages. To explore the origins and evolution of chromosome numbers and genome size in ferns, we used flow cytometry to measure the genomes of 240 species (255 samples) of extant ferns and lycophytes comprising 27 families and 72 genera, of which 228 species (242 samples) represent new reports. We analyzed correlations among genome size, spore size, chromosomal features, phylogeny, and habitat type preference within a phylogenetic framework. We also applied ANOVA and multinomial logistic regression analysis to preference of habitat type and genome size. Using the phylogeny, we conducted ancestral character reconstruction for habitat types and tested whether genome size changes simultaneously with shifts in habitat preference. We found that 2C values had weak phylogenetic signal, whereas the base number of chromosomes (x) had a strong phylogenetic signal. Furthermore, our analyses revealed a positive correlation between genome size and chromosome traits, indicating that the base number of chromosomes (x), chromosome size, and polyploidization may be primary contributors to genome expansion in ferns and lycophytes. Genome sizes in different habitat types varied significantly and were significantly correlated with habitat types; specifically, multinomial logistic regression indicated that species with larger 2C values were more likely to be epiphytes. Terrestrial habitat is inferred to be ancestral for both extant ferns and lycophytes, whereas transitions to other habitat types occurred as the major clades emerged. Shifts in habitat types appear be followed by periods of genomic stability. Based on these results, we inferred that habitat type changes and multiple whole-genome duplications have contributed to the formation of large genomes of ferns and their allies during their evolutionary history.

Born to Win: Reproductive Health Policy and Urban Education Returns in China.

This study explores the relationship between China's reproductive health policy and the rate of return on urban education by using fixed-effect, mediating-effect, and breakpoint regression models. The authors study the impact of China's reproductive health policy on individual years of education, income, return on education, the impact of reproductive health policy on population health, and overall human development. The empirical results show that the implementation of China's reproductive health policy can improve the rate of return on urban education and increase the average length of education of urban residents by 0.29 years. Under the breakpoint regression model, the educational return rate of urban residents is approximately 12.2% higher than the ordinary least squares (OLS) estimate. China's reproductive health policy has significantly promoted the return rate of residents' education and simultaneously effectively promoted the income of urban residents. With the development of the economy, the government should properly adjust reproductive health policies and improve the population health rate so that the adjustment of reproductive health policies can comprehensively promote the health of residents of all ages. The overall relaxation of family restrictions on children's human capital investment will likely reduce the negative impact of the overall relaxation of family planning, not only improving the health of the population but also contributing to sustainable economic development.

Thyroid Function and Low Free Triiodothyronine in Chinese Patients With Autoimmune Encephalitis.

Background and Objectives: Low free triiodothyronine (FT3) is usually associated with worse functional outcome in critical illness; however, the information on thyroid dysfunction and autoimmune encephalitis (AE) is limited. This study aims to evaluate the clinical prognostic value of thyroid function and low-T3 syndrome in patients with multiple subtypes of AE. Methods: In this retrospective study, we identified the hospital records of 319 candidate patients with AE admitted between January 2016 and December 2020. We then extracted the clinical features and outcomes. Modified Rankin scale (mRS) scores were used to evaluate the patients' neurological function. The serum levels of FT3, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured upon admission. Normal thyroid stimulating hormone level with FT3 below the lower limit of the reference interval (2.63 nmol/L) was defined as low-T3 syndrome. Results: A total of 237 AE cases remained after screening. Among these, 57.81% (137/237) were men and the average age at onset was 41 y (interquartile range, 12-61 y). We found that 83.54% (198/237) of the patients had a good prognosis, and 16.46% (39/237) had a poor prognosis. Abnormal thyroid function was observed in 30.80% of these patients, with a relatively greater prevalence in the group with a poor prognosis (p < 0.001). The serum FT3 levels in the poor-prognosis group were significantly lower than those in the good-prognosis group (p < 0.001). Low-T3 syndrome occurred in 15.19% of AE cases and was more frequent in patients with poor prognosis (p < 0.001). Conclusions: Abnormal thyroid function in AE is frequent, and serum FT3 levels in patients with poor prognosis are significantly lower than in those with good prognosis. Low-T3 syndrome could be a potential candidate for predicting the prognosis of AE following future research.

Effect of integrated Traditional Chinese and Western Medicine on gout.

OBJECTIVE: To evaluate the curative effect of integrated Traditional Chinese and Western Medicine on gout, and to investigate the therapy timing and exact treatment options of integrated medicine. METHODS: Totally 860 patients were enrolled, including 460 patients with intermittent gout, 200 patients with active Traditional Chinese Medicine (TCM) syndrome (TCM syndrome score ≥ 6) and 200 patients with stable TCM syndrome (score < 6). They were randomly divided into intervention and control groups. The control group was treated according to Western Medicine guidelines. The intervention group was treated with integrated Traditional Chinese and Western Medicine. The efficacy of TCM syndrome, joint pain score, joint swelling score, ESR, C-reactive protein, serum uric acid, liver and kidney function, and the duration of remission of TCM syndrome were compared between the two groups before and after treatments. RESULTS: For the patients with stable TCM syndrome, there was no significant difference in the effective rate and inefficiency between the intervention group and the control group. For the active type, the effective rate of the intervention group is better than the control group significantly. For the stable type, there was no significant difference between the intervention group and the control group in improving the scores of joint pain and swelling, reducing the level of ESR, C-reactive protein, serum uric acid and improving liver and kidney function. For the active type, the differences between the two groups were significant. The stable stage of gout in the intervention group was longer than the control group. CONCLUSION: For the gout patients with stable TCM syndrome in the acute stage of gout, we can use TCM treatment or Western Medicine alternatively; for the patients with active TCM syndrome, the scheme of combination of Traditional Chinese and Western Medicine can be applied, with the better curative effect than any medicine alone.

Nomogram for hepatic venous pressure gradient in patients with cirrhosis.

OBJECTIVE: The hepatic venous pressure gradient (HVPG) plays an important role in the treatment and prognosis of patients with cirrhosis. Our study aimed to develop and validate a nomogram for an HVPG >12 mmHg. METHODS: A retrospective study was performed to create a nomogram for an HVPG >12 mmHg in a training cohort that was validated in another cohort. The discriminatory ability and calibration of the nomogram were tested using the C-statistic, area under the receiver operating characteristic curve (AUROC) and calibration plots. RESULTS: The nomogram was based on portosystemic shunts identified on computed tomography images, the etiology of cirrhosis and the Child-Pugh grade. These parameters were significantly associated with an HVPG >12 mmHg (P < 0.05 for both the training and validation cohorts). In the training cohort, the model showed good discrimination (C-statistic, AUROC, and R2 of 0.71, 0.71 and 0.13, respectively) and good calibration. The total cutoff value was 112 and the sensitivity and specificity were 57.1% and 77.6%, respectively. The application of the nomogram in the validation cohort still yielded good discrimination (C-statistic 0.75 [95% confidence interval 0.61-0.89], AUROC 0.75, and R2 0.16) and good calibration. CONCLUSIONS: This nomogram is a convenient tool for predicting an HVPG >12 mmHg in patients with cirrhosis and can help clinicians quickly identify patients with decompensated cirrhosis.

The complete chloroplast genome of Plateau herb Chesneya acaulis (Fabaceae).

Chesneya acaulis is a perennial herb, which restricts in Xizang (Tibet) of China, Afghanistan, and Pakistan. The complete chloroplast genome was sequenced using the Illumina Hiseq X-Ten platform. The genome lacks an inverted repeat (IR) region, containing 75 protein-coding genes, 29 tRNAs genes, and 4 rRNAs. The overall GC content is 34.6%. A phylogenetic tree based on the whole chloroplast genomes of 15 species indicated that C. acaulis had a close relationship with the genus Hedysarum, and it nested in the inverted repeat-lacking clade (IRLC), of the subfamily Papilionoideae (Leguminosae).

Expression of apolipoprotein C1 in clear cell renal cell carcinoma: An oncogenic gene and a prognostic marker.

This study aimed to explore whether APOC1 expression has a function in the biological behavior of clear cell renal cell carcinoma (ccRCC) cells and its possible mechanism. Bioinformatics analysis of data TCGA and OnComine was conducted to explore the expression pattern and prognostic value of APOC1, as well as the relationship between APOC1 expression and clinical indicators. Loss- and gain- of APOC1 function assays were carried out to assess the biological functions of APOC1. Western blotting was applied to detect protein expression. We revealed that APOC1 was upregulated in ccRCC tissues. APOC1 expression was related to gender, grade, pathologic-T, pathologic-stage, and pathologic-M in patients with ccRCC. Meanwhile, Kaplan-Meier analysis evidenced that the high APOC1 expression indicated unfavorable outcomes of ccRCC. Functional experiments in vitro revealed that upregulation of APOC1 in UT33A cells promoted cell proliferation, invasion, and migration, while downregulation of APOC1 in 786-O cells had the opposite effect. Furthermore, epithelial mesenchymal transition (EMT) was activated in cells with upregulated APOC1 but inhibited in cells with down-regulated APOC1. Collectively, our data suggested that APOC1 was overexpressed in ccRCC cells and promoted the malignant biological behaviors and EMT of ccRCC cells.

Birth experiences of urban women of advanced age having their second child after introduction of the universal two-child policy in China: A qualitative study.

OBJECTIVE: to investigate the birth experiences of women of advanced age having a second child in urban China after introduction of the universal two-child policy in 2016. DESIGN: data were collected using semi-structured in-depth interviews, and were processed and analysed using a qualitative phenomenological method. SETTING: obstetric department of a class 1, level 3 hospital in Henan Province, China. PARTICIPANTS: purposive sampling was undertaken, and 11 hospitalized women from urban backgrounds were selected as the participants. They were all aged >35 years and were having their second child. The interviews were conducted 2-4 days post partum. FINDINGS: the findings were divided into four themes: motives for the birth of a second child; anticipations for the child's gender; difficulty in conceiving; and conflicts after birth. The main reason for having a second child was no longer in accordance with the traditional Chinese mindset to 'raise sons to secure a happy life when one gets old'; instead, it was to secure family balance and harmony to respond to the new policy. Educated women from urban backgrounds were able to accept the gender of the second child 'as it came', without the old mindset that 'men are superior to women' and 'only boys can carry on family lines'. Advanced maternal age and gestational complications were the major difficulties facing these women. Chinese medicine and regimens were recognised as effective and conducive. Following the birth of their second child, the women experienced both positive feelings (joy due to the arrival of the new baby) and negative feelings (pressures and challenges on family finances, demands for more living space, and balancing their affections between two children). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: women of advanced age who choose to have a second child have sensible motives and, for the most part, their experience is positive. That said, the participants faced and overcame many difficulties before, during and after the birth of their second child. They were in need of help from the government and their employers in terms of policy, and proper education on care-taking and recuperation from medical professionals. Families who have a second child should treat the second child calmly and with common sense, make quick adjustments to family structural changes, and strike a proper balance in an effort to divide love and care equally between the two children.

Tumor necrosis factor alpha mediates neuromuscular synapse elimination.

During the development of mammalian neuromuscular junction (NMJ), the original supernumerary axon inputs are gradually eliminated, finally leaving each muscle fiber innervated by a single axon terminal. However, the molecular cues that mediate the elimination of redundant axon inputs remain unclear. Here we show that tumor necrosis factor-α (TNFα) expressed in postsynaptic muscle cells plays an important role in presynaptic axonal elimination at the NMJ. We found that intramuscular injection of TNFα into the levator auris longus (LAL) muscles caused disassociation of presynaptic nerve terminals from the postsynaptic acetylcholine receptor (AChR) clusters. By contrast, genetic ablation of TNFα globally or specifically in skeletal muscle cells, but not in motoneurons or Schwann cells, delayed the synaptic elimination. Moreover, ablation of TNFα in muscle cells attenuated the tendency of activity-dependent competition in a motoneuron-muscle coculture system. These results suggest a role of postsynaptic TNFα in the elimination of redundant synaptic inputs.

The complete chloroplast genome of desert spiny semi-shrub Alhagi sparsifolia (Fabaceae) from Central Asia.

Alhagi sparsifolia is a sand-resistant subshrub and food resource for camels in the desert and semi-desert areas of Central Asia. In China, this is the olny Alhagi species and it is restricted in the Northwestern region. Its complete chloroplast genome was sequenced using the Illumina Hiseq X-Ten platform. The genome lacks an inverted repeat (IR) region, containing 74 protein-coding genes, 30 tRNAs genes, and four rRNAs. The overall GC content is 43.6%. Based on the chloroplast genome sequence, a maximum-likelihood (ML) tree was constructed along with its 15 taxa, indicating that A. sparsifolia belong to the tribe Hedysareae, which nested in IRLC group of the subfamily Papilionoideae (Fabaceae).

Down-regulation of long non-coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up-regulation of microRNA-204.

Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA-204 (miR-204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR-204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR-204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR-204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR-204 with siRNA against HOTAIR, miR-204 mimic or miR-204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR-204 was down-regulated, while HOTAIR and HOXC8 were up-regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR-204 and miR-204 could further target HOXC8. The oesophageal cancer cells treated with si-HOTAIR or miR-204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP-9, but increased E-cadherin level. Silenced HOTAIR or elevated miR-204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR-204 as a competing endogenous RNA and regulate miR-204 and HOXC8. Hence, down-regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.

Long Non-Coding RNA (lncRNA) X-Inactive Specific Transcript (XIST) Plays a Critical Role in Predicting Clinical Prognosis and Progression of Colorectal Cancer.

BACKGROUND Long non-coding RNAs (lncRNAs) participate in all cancer biology processes of cells. Although functions and associated mechanisms of lncRNAs have been proven in colorectal cancer (CRC), the roles of lncRNA X-inactive specific transcript (XIST) have not been clearly investigated in CRC. MATERIAL AND METHODS Expression of XIST was detected by quantitative real-time PCR (qRT-PCR) assay in CRC cell lines and 196 clinical samples. Correlations between XIST expression and CRC clinicopathological features were analyzed. Log-rank test and Kaplan-Meier test were performed to assess and compare the prognoses of patients with higher and lower expression of XIST. The multivariate Cox regression and univariate Cox regression were conducted to evaluate the risk factors for prognosis of CRC. RESULTS lncRNA XIST was upregulated in CRC cells lines and tissues (p<0.05). Statistical analysis found high XIST expression was correlated with larger tumor size, N1, M1, and topography lymph node metastasis (TNM) III+IV stage of CRC. Moreover, higher expression of XIST could predict poor progression-free survival (PFS) and poor overall survival (OS) of CRC patients. The M1 stage and high expression of XIST were proven to be independent risk factors for poor prognosis (p<0.05). CONCLUSIONS XIST is upregulated in CRC and is significantly correlated with CRC clinical progression. lncRNA XIST overexpression predict poor PFS and poor OS for CRC patients. lncRNA XIST can be an independent risk factor for CRC prognosis, and could be a potential therapeutic target and prognostic biomarker for CRC patients.

Ginsenoside Rb1 protects dopaminergic neurons from inflammatory injury induced by intranigral lipopolysaccharide injection.

Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson's disease. As such, inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson's disease. Ginsenoside Rb1, the most active ingredient of ginseng, reportedly exerts neuroprotective effects by suppressing inflammation in vitro. The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rb1 in a lipopolysaccharide-induced rat Parkinson's disease model. Rats were divided into four groups. In the control group, sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days. In the ginsenoside Rb1 group, ginsenoside Rb1 (20 mg/kg) was intraperitoneally injected for 14 consecutive days after sham surgery. In the lipopolysaccharide group, a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson's disease model. Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days. In the ginsenoside Rb1 + lipopolysaccharide group, lipopolysaccharide was unilaterally microinjected into the rat substantial nigra. Subsequently, ginsenoside Rb1 was intraperitoneally injected for 14 consecutive days. To investigate the therapeutic effects of ginsenoside Rb1, behavioral tests were performed on day 15 after lipopolysaccharide injection. We found that ginsenoside Rb1 treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group. To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rb1, contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography. Compared with the lipopolysaccharide group, ginsenoside Rb1 obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites in the striatum. To further explore the neuroprotective effect of ginsenoside Rb1 against lipopolysaccharide-induced neurotoxicity, immunohistochemistry and western blot assay of tyrosine hydroxylase were performed to evaluate dopaminergic neuron degeneration in the substantial nigra par compacta. The results showed that lipopolysaccharide injection caused a large loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a significant decrease in overall tyrosine hydroxylase expression. However, ginsenoside Rb1 noticeably reversed these changes. To investigate whether the neuroprotective effect of ginsenoside Rb1 was associated with inhibition of lipopolysaccharide-induced microglial activation, we examined expression of the microglia marker Iba-1. Our results confirmed that lipopolysaccharide injection induced a significant increase in Iba-1 expression in the substantia nigra; however, ginsenoside Rb1 effectively suppressed lipopolysaccharide-induced microglial overactivation. To elucidate the inhibitory mechanism of ginsenoside Rb1, we examined expression levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and cyclooxygenase 2) and phosphorylation of nuclear factor kappa B signaling-related proteins (IκB, IKK) in the substantia nigra with enzyme-linked immunosorbent and western blot assays. Our results revealed that compared with the control group, phosphorylation and expression of inflammatory mediators IκB and IKK in the substantia nigra of lipopolysaccharide group rats were significantly increased; whereas, ginsenoside Rb1 obviously reduced lipopolysaccharide-induced changes on the lesioned side of the substantial nigra par compacta. These findings confirm that ginsenoside Rb1 can inhibit inflammation induced by lipopolysaccharide injection into the substantia nigra and protect dopaminergic neurons, which may be related to its inhibition of the nuclear factor kappa B signaling pathway. This study was approved by the Experimental Animal Ethics Committee of Shandong University of China in April 2016 (approval No. KYLL-2016-0148).