Comparative mitochondrial genomics in Nematoda reveal astonishing variation in compositional biases and substitution rates indicative of multi-level selection.

BACKGROUND: Nematodes are the most abundant and diverse metazoans on Earth, and are known to significantly affect ecosystem functioning. A better understanding of their biology and ecology, including potential adaptations to diverse habitats and lifestyles, is key to understanding their response to global change scenarios. Mitochondrial genomes offer high species level characterization, low cost of sequencing, and an ease of data handling that can provide insights into nematode evolutionary pressures. RESULTS: Generally, nematode mitochondrial genomes exhibited similar structural characteristics (e.g., gene size and GC content), but displayed remarkable variability around these general patterns. Compositional strand biases showed strong codon position specific G skews and relationships with nematode life traits (especially parasitic feeding habits) equal to or greater than with predicted phylogeny. On average, nematode mitochondrial genomes showed low non-synonymous substitution rates, but also high clade specific deviations from these means. Despite the presence of significant mutational saturation, non-synonymous (dN) and synonymous (dS) substitution rates could still be significantly explained by feeding habit and/or habitat. Low ratios of dN:dS rates, particularly associated with the parasitic lifestyles, suggested the presence of strong purifying selection. CONCLUSIONS: Nematode mitochondrial genomes demonstrated a capacity to accumulate diversity in composition, structure, and content while still maintaining functional genes. Moreover, they demonstrated a capacity for rapid evolutionary change pointing to a potential interaction between multi-level selection pressures and rapid evolution. In conclusion, this study helps establish a background for our understanding of the potential evolutionary pressures shaping nematode mitochondrial genomes, while outlining likely routes of future inquiry.

Exploring the use of metabarcoding to reveal eukaryotic associations with mononchids nematodes.

Nematodes play a vital ecological role in soil and marine ecosystems, but there is limited information about their dietary diversity and feeding habits. Due to methodological challenges, the available information is based on inference rather than confirmed observations. The lack of correct dietary requirements also hampers rearing experiments. To achieve insight into the prey of mononchid nematodes, this study employed high-throughput Illumina paired-end sequencing using universal eukaryotic species 18S primers on 10 pooled mononchid nematode species, namely Mylonchulus brachyuris, M. brevicaudatus, Mylonchulus sp., Clarkus parvus, Prionchulus sp. M. hawaiiensis, M. sigmaturellus, M. vulvapapillatus, Anatonchus sp. and Miconchus sp. The results indicate that mononchids are associated with a remarkable diversity of eukaryotes, including fungi, algae, and protists. While the metabarcoding approach, first introduced here for mononchids, proved to be a simple and rapid method, it has several limitations and crucial methodological challenges that should be addressed in future studies. Ultimately, such methods should be able to evaluate the dietary complexity of nematodes and provide a valuable avenue for unraveling the dietary requirements of previously unculturable nematodes. This can contribute to the methodology of understanding their feeding habits and contributions to ecosystem dynamics.

TEM Investigation on the Dislocation Loops in Zirconium Alloy by Neutron and Kr+ Ion Irradiation Tests.

Neutron irradiation (E ≥ 1 MeV) and 400 keV Kr+ ion irradiation tests were carried out and compared to study the formation and growth mechanism of dislocation loops in zirconium alloys. The results show that, as the irradiation reached 1.9 × 1025 n/m2 and 1.0 × 1020 Kr+/m2, a large number of -type dislocation loops and a small amount of large-sized -type dislocations hundreds of nanometers or even micrometers in size are observed in both samples. EDS results confirmed that the concentrations of Nb and Fe in the -type dislocation loops are higher than that in the matrix. With the increases of the dislocation loop size, part of the loop structure will decompose into the twisted, small-sized dislocation lines. Between two of the small-sized dislocation lines, a cubic structure was observed.

Livestock grazing modifies soil nematode body size structure in mosaic grassland habitats.

Body size is closely related to the trophic level and abundance of soil fauna, particularly nematodes. Therefore, size-based analyses are increasingly prominent in unveiling soil food web structure and its responses to anthropogenic disturbances, such as livestock grazing. Yet, little is known about the effects of different livestock on the body size structure of soil nematodes, especially in grasslands characterized by local habitat heterogeneity. A four-year field grazing experiment from 2017 to 2020 was conducted in a meadow steppe characterized by typical mosaics of degraded hypersaline patches and undegraded hyposaline patches to assess the impacts of cattle and sheep grazing on the body size structure of soil nematodes within and across trophic groups. Without grazing, the hypersaline patches harbored higher abundance of large-bodied nematodes in the community compared to the hyposaline patches. Livestock grazing decreased large-bodied nematodes within and across trophic groups mainly by reducing soil microbial biomass in the hypersaline patches, with sheep grazing resulting in more substantial reductions compared to cattle grazing. The reduction in large-bodied nematode individuals correspondingly resulted in decreases in nematode community-weighted mean (CWM) body size, nematode biomass, and size spectra slopes. However, both cattle and sheep grazing had minimal impacts on the CWM body size and size spectra of total nematodes in the hyposaline patches. Our findings suggest that livestock grazing, especially sheep grazing, has the potential to simplify soil food webs by reducing large-bodied nematodes in degraded habitats, which may aggravate soil degradation by weakening the bioturbation activities of soil fauna. In light of the widespread land use of grasslands by herbivores of various species and the ongoing global grassland degradation of mosaic patches, the recognition of the trends revealed by our findings is critical for developing appropriate strategies for grassland grazing management.

BFGF attenuates aortic valvular interstitial cell calcification by inhibiting endoplasmic reticulum stress-mediated apoptosis.

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy.

[Characteristics and Influencing Factors of Greenhouse Fluxes from Urban Lawn].

As an important component of urban green spaces, greenhouse gas uptake or emissions from urban lawns cannot be ignored. However, studies of greenhouse gas fluxes from subtropical urban lawns are relatively sparse. The static chamber-gas chromatography method was applied to monitor the ground-air exchange fluxes of various greenhouse gases(CO2, CH4, N2O, and CO) in typical urban lawns of Hangzhou City. Our results showed that the average fluxes had significant seasonal cycles but ambiguous diurnal variations. The grassland and the soil(naked soil without vegetation coverage) acted as sources of atmospheric N2O, with the average fluxes of (0.66±0.17) and (0.58±0.20) µg·(m2·min)-1 for N2O, respectively; however, they were also sinks of CH4 and CO, with the average fluxes of (-0.21±0.078) and (-0.26±0.10) µg·(m2·min)-1 for CH4 and (-6.36±1.28) and (-6.55±1.69) µg·(m2·min)-1 for CO, respectively. The average CO2emission fluxes of urban grassland and soil were(5.28±0.75) and (4.83±0.91) mg·(m2·min)-1, respectively. The correlation analysis indicated that the CO2 and N2O fluxes of grassland and soil were negatively correlated with precipitation, whereas the CH4 and CO fluxes were positively correlated with it. There was no significant correlation between grassland CH4 fluxes and soil temperature, and N2O fluxes had a significant negative correlation with soil temperature; the other greenhouse gas fluxes showed a significant positive correlation with soil temperature. In addition, the seasonal variation in CO2 (R2=0.371 and 0.314) and N2O(R2=0.371 and 0.284) fluxes from both grassland and soil was affected by precipitation, whereas CO fluxes (R2=0.290 and 0.234) were mainly driven by soil temperature compared with the other greenhouse gases.

A c-di-GMP binding effector controls cell size in a cyanobacterium.

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule. It is also a critical player in the regulation of cell size and cell behaviors such as cell aggregation and phototaxis in cyanobacteria, which constitute an important group of prokaryotes for their roles in the ecology and evolution of the Earth. However, c-di-GMP receptors have never been revealed in cyanobacteria. Here, we report the identification of a c-di-GMP receptor, CdgR, from the filamentous cyanobacterium Anabaena PCC 7120. Crystal structural analysis and genetic studies demonstrate that CdgR binds c-di-GMP at the dimer interface and this binding is required for the control of cell size in a c-di-GMP-dependent manner. Different functions of CdgR, in ligand binding and signal transmission, could be separated genetically, allowing us to dissect its molecular signaling functions. The presence of the apo-form of CdgR triggers cell size reduction, consistent with the similar effects observed with a decrease of c-di-GMP levels in cells. Furthermore, we found that CdgR exerts its function by interacting with a global transcription factor DevH, and this interaction was inhibited by c-di-GMP. The lethal effect triggered by conditional depletion of DevH or by the production of several point-mutant proteins of CdgR in cells indicates that this signaling pathway plays critical functions in Anabaena. Our studies revealed a mechanism of c-di-GMP signaling in the control of cell size, an important and complex trait for bacteria. CdgR is highly conserved in cyanobacteria, which will greatly expand our understanding of the roles of c-di-GMP signaling in these organisms.

Intracardiac paraganglioma with a cough as the first symptom.

BACKGROUND: Cardiac paragangliomas (PGLs) are clinically rare, with hypertension and metabolic changes as the main symptoms. The tumor is highly related to gene mutation, and surgery is presently the effective treatment. Medical history and clinical manifestations of the patient, routine laboratory examinations and imaging examinations, and pathological examination can help the final diagnosis. CASE PRESENTATION: The present study presents a 31-year-old male patient with a left atrial mass. The initial symptom was cough. Cardiac enlargement was found during the chest X-ray. The follow-up imaging examination revealed a left atrial occupying lesion, and the possibility of malignant occupying lesions was not ruled out. The patient underwent surgical resection of the mass. The final pathological result revealed paraganglioma. The thoracic computed tomography review two months after the operation revealed that the original occupying lesion disappeared, and no new lesion was found. CONCLUSIONS: Pheochromocytomas and paragangliomas (PPGLs) are a kind of neuroendocrine tumors. PPGLs can cause secondary hypertension, and lead to a series of clinical syndromes, including myocardial injury, metabolic changes, and so on. The occurrence of PPGIs is related to gene mutation. Biochemical detection, imaging examination, and genetic testing can help diagnose. The tumor should be surgically removed as soon as possible after the diagnosis. As a functional tumor, PPGLs should be fully prepared before surgery to avoid anesthesia and huge fluctuations in blood pressure during and after surgery, or the occurrence of fatal hypertensive crisis and intractable hypotension after tumor resection. Adequate preoperative preparation directly affects the prognosis of patients after surgery. Therefore, multidisciplinary cooperation before, during, and after the operation is extremely important.

Domestic and international researches related to postpartum rehabilitation in the last decade: a visualized analysis / 中国康复理论与实践

ObjectiveTo analyze the research hotspots and development trends of postpartum rehabilitation at home and abroad in the past ten years. MethodsCiteSpace 6.2.R2 was used to analyze the co-occurrence, cluster, and bursting of keywords of the relevant literature in the field of postpartum rehabilitation in CNKI and Web of Science (WOS) in the past ten years. ResultsTotally, 2 686 Chinese papaers were included in CNKI and 1 247 English papers were included in WOS. Both databases showed an increasing trend in the number of publications related to the field of postpartum rehabilitation, but the overall number of publications in CNKI grew faster and the total number of publications was more than that in WOS. For CNKI, there were 455 nodes, 1 102 links, with a density of 0.010 7; nine clusters were obtained; the bursting keywords showed that the diseases of concern shifted from breast distension and pain to pelvic floor diseases, and the hot spots of treatment methods shifted from Chinese medicine to electrical stimulation, biofeedback, and then pelvic floor training. For WOS, there were 463 nodes, 1 633 connected lines, with a density of 0.015 3; 14 clusters were obtained; the bursting keywords showed that the disease hotspots of concern shifted from anal prolapse and postpartum hemorrhage to organ prolapse, the hotspots of treatment methods shifted from analgesia to exercise, and the focus of research methods shifted from trial to qualitative research and meta-analysis. ConclusionDomestic postpartum rehabilitation started later than foreign countries. Although certain research results have been achieved, there is still a certain gap compared with the development of foreign postpartum rehabilitation.

Governor vessel moxibustion combined with western medication for mild to moderate depression with kidney-yang deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the therapeutic efficacy of governor vessel moxibustion combined with fluoxetine hydrochloride capsule, simple fluoxetine hydrochloride capsule and placebo moxibustion combined with fluoxetine hydrochloride capsule for mild to moderate depression with kidney-yang deficiency.@*METHODS@#A total of 126 patients with mild to moderate depression with kidney-yang deficiency were randomized into a governor vessel moxibustion group (42 cases, 2 cases dropped off), a western medication group (42 cases, 1 case dropped off) and a placebo moxibustion group (42 cases, 1 case dropped off). The western medication group was given fluoxetine hydrochloride capsule orally, 20 mg a time, once a day. On the basis of the treatment in the western medication group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the governor vessel moxibustion group, once a week; placebo moxibustion was applied in the placebo moxibustion group, once a week. Treatment of 8 weeks was required in the 3 groups. Before and after treatment, the scores of Hamilton depression scale-17 (HAMD-17), Asberg's rating scale for side effects (SERS) and TCM clinical symptom were compared, and the clinical efficacy was evaluated.@*RESULTS@#After treatment, the scores of HAMD-17, SERS and TCM clinical symptom were decreased compared before treatment in the 3 groups (P<0.05), the decrease ranges of above scores in the governor vessel moxibustion group were larger than those in the western medication group and the placebo moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the governor vessel moxibustion group, which was higher than 75.6% (31/41) in the western medication group and 80.5% (33/41) in the placebo moxibustion group (P<0.05).@*CONCLUSION@#Governor vessel moxibustion combined with fluoxetine hydrochloride capsule can improve the degree of depression and relieve the clinical symptoms in mild to moderate depression patients with kidney-yang deficiency, the efficacy is superior to simple fluoxetine hydrochloride capsule, and can reduce the fluoxetine hydrochloride capsule-induced adverse effect to a certain extent.

Evaluation of p16/Ki-67 double-stained immunohistochemistry in diagnosis of human papilloma virus-positive oropharyngeal squamous cell carcinoma / 中华口腔医学杂志

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

Research Progress on Epigenetics in Endometriosis / 中国医学科学院学报

Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.

Complete Mitogenome of Cruznema Tripartitum Confirms Highly Conserved Gene Arrangement within Family Rhabditidae.

Mitochondrial genomes have widely been used as molecular markers in understanding the patterns and processes of nematode evolution. The species in genus Cruznema are free-living bacterivores as well as parasites of crickets and mollusks. The complete mitochondrial genome of C. tripartitum was determined through high-throughput sequencing as the first sequenced representative of the genus Cruznema. The genome is comprised of 14,067 bp nucleotides, and includes 12 protein-coding, two rRNA, and 22 tRNA genes. Phylogenetic analyses based on amino acid data support C. tripartitum as a sister to the clade containing Caenorhabditis elegans and Oscheius chongmingensis. The analysis of gene arrangement suggested that C. tripartitum shares the same gene order with O. chongmingensis, Litoditis marina, Diplocapter coronatus, genus Caenorhabditis, and Pristionchus pacificus. Thus, the mitochondrial gene arrangement is highly conserved in the family Rhabditidae as well as some species in Diplogasteridae.

Phylogeography of Chinese cereal cyst nematodes sheds lights on their origin and dispersal.

Reconstructing the dispersal routes of pathogens can help identify the key drivers of their evolution and provides a basis for disease control. The cereal cyst nematode Heterodera avenae is one of the major nematode pests on cereals that can cause 10%-90% crop yield losses worldwide. Through extensive sampling on wheat and grasses, the Chinese population of H. avenae is widely identified in virtually all wheat growing regions in China, with H1 being the predominant haplotype. The monoculture of wheat in north China might have been the key driver for the prevalence of H1 population, which should date no earlier than the Han Dynasty (202 BCE-220 CE). Molecular phylogenetic and biogeographic analyses of Chinese H. avenae suggest a Pleistocene northwest China origin and an ancestral host of grasses. We assume that the prosperity of Heterodera in this region is a result of their preference for cooler climate and various grass hosts, which only appeared after the uplift of Qinghai-Tibetan Plateau and aridification of Inner Asia. Nematode samples from the current and historical floodplains show a significant role of the Yellow River in the distribution of Chinese H. avenae. Whereas mechanical harvesters that operate on an inter-provincial basis suggest the importance in the transmission of this species in eastern China in recent times. This study highlights the role of environmental change, river dynamics, and anthropogenic factors in the origin and long-distance dissemination of pathogens.

[A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation. RESULTS: CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1). CONCLUSION: The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1/α-KG-mediated glycolysis.

Hepatic stellate cells (HSCs) play an important role in the initiation and development of liver fibrogenesis, and abnormal glucose metabolism is increasingly being considered a crucial factor controlling phenotypic transformation in HSCs. However, the role of the factors affecting glycolysis in HSCs in the experimental models of liver fibrosis has not been completely elucidated. In this study, we showed that glycolysis was significantly enhanced, while the expression of brain and muscle arnt-like protein-1 (Bmal1) was downregulated in fibrotic liver tissues of mice, primary HSCs, and transforming growth factor-ß1 (TGF-ß1)-induced LX2 cells. Overexpression of Bmal1 in TGF-ß1-induced LX2 cells blocked glycolysis and inhibited the proliferation and phenotypic transformation of activated HSCs. We further confirmed the protective effect of Bmal1 in liver fibrosis by overexpressing Bmal1 from hepatic adeno-associated virus 8 in mice. In addition, we also showed that the regulation of glycolysis by Bmal1 is mediated by the isocitrate dehydrogenase 1/α-ketoglutarate (IDH1/α-KG) pathway. Collectively, our results indicated that a novel Bmal1-IDH1/α-KG axis may be involved in regulating glycolysis of activated HSCs and might hence be used as a therapeutic target for alleviating liver fibrosis.

Promoter analysis of TLR5M and TLR5S revealed NF-κB might be a conserved cis-element in TLR5S promoter of large yellow croaker.

Toll like receptor 5 (TLR5) plays a crucial role in the innate immune response by recognizing bacterial flagellin proteins. In the present study, the genomic and 5'-flanking sequences of LcTLR5M (membrane) and LcTLR5S (soluble) were cloned from the large yellow croaker, Larimichthys crocea. Then, their promoter activities were determined in human embryonic kidney (HEK293T) cells. LcTLR5M contained 4 exons and 3 introns, and LcTLR5S contained 2 exons and 1 intron. Bioinformatic prediction of transcription factor binding sites (TFBSs) indicated that the promoter structures were different between LcTLR5M and LcTLR5S. A dual luciferase assay showed that the deletion mutant -471 to +189 of LcTLR5M promoter possessed the greatest activity with 36 times activity of the control (P < 0.05). For LcTLR5S, two deletion mutants, -1687 to +106 and - 720 to +106, showed high promoter activity. Furthermore, site-directed mutation demonstrated that a -392 to -391 AT/GG substitution in Oct-1 binding site, and a -104 to -103 GG/TT and a -98 to -97 CC/AA substitution in the NF-κB binding site of TLR5S caused a significant decline of luciferase activity (P < 0.05). Moreover, the co-transfection of an NF-κB/p65 over-expression plasmid with wild type TLR5S (-720 to +106) resulted in an extremely significant increase of promoter activity by more than 9 times compared with the NF-kB mutant (P < 0.01). Our findings suggest that the genomic organization and promoter structure may differ between LcTLR5M and LcTLR5S. Oct1 and NF-κB binding sites might be cis-regulatory elements in the LcTLR5S promoter. NF-κB/p65 plays an important role in LcTLR5S promoter activation through binding with the NF-κB binding site.

The predictive value of HEART score combined with NT-proBNP for cardiovascular adverse events in patients with non-ST-elevation acute coronary syndrome / 中华急诊医学杂志

Objective:To explore the predictive value of HEART score combined with N-terminal pro-B-type natriuretic peptides (NT-proBNP) for 3-month major adverse cardiovascular events (MACE) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).Methods:This was a retrospective cohort study. Adult patients with acute chest pain who met the diagnostic criteria for NSTE-ACS in the 5th Affiliated Hospital of Sun Yat-Sen University from January 2018 to March 2018 were enrolled. Patients with cardiac chest pain caused by diseases other than NSTE-ACS, non-cardiac chest pain, renal insufficiency, acute cerebral infarction, end-stage disease, pregnant, and incomplete data were excluded. Data of all patients’ general clinical information, first electrocardiogram (ECG), cardiac troponin I (cTnI), and NT-proBNP were collected. The correlation between NT-proBNP level and the occurrence of MACE within 3 months was analyzed. The receiver operating characteristic (ROC) curves was drawn, and the predictive value of NT-proBNP, HEART score, and their combination for 3- month MACE in patients with NSTE-ACS were evaluated.Results:A total of 151 patients were enrolled. Patients with NSTE-ACS were divided into the MACE group ( n=95) and non-MACE group ( n=56) according to whether MACE occurred within 3 months of onset. The level of NT-proBNP, the HEART score, and the cTnI level in the MACE group were significantly higher than those in the non-MACE group (all P<0.001). After risk stratification assessed by HEART score in all patients with NSTE-ACS, it was found that the level of NT-proBNP and the incidence of MACE increased as the risk score increased (all P<0.05). The area under the ROC curve of HEART score, NT-proBNP and their combination were 0.819 (95% CI:0.751-0.887), 0.821 (95% CI:0.752-0.889) and 0.858 (95% CI:0.796-0.919), respectively. Conclusions:The combination of HEART score and NT-proBNP level can improve the predictive value for 3-month MACE in patients within NSTE-ACS, and provide important information for treatment decision and improving prognosis.