Selective modulation of alkali metal ions on acetylcholinesterase.

Acetylcholinesterase (AChE) is an important hydrolase in cholinergic synapses and a candidate target in the treatment of Alzheimer's disease. The lithium treatment widely used in neurological disorders can alter the AChE activity, yet the underlying mechanism of how the ion species regulate the enzymatic activity remains unclear. In this work, we performed combined quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) simulations and well-tempered metadynamics to understand the modulation of human AChE (hAChE) activity using three alkali metal ions (Li+, Na+, and K+) in different concentrations. Our simulations show that the binding affinity and catalytic activity are affected by different ion species through allosteric ion coordination geometries on the hAChE complex and distant electrostatic screening effect. A Li+ cluster involving D330, E393, and D397 residues and three Li+ ions was found to be highly conserved and can be critical to the enzyme activity. Binding energy calculations indicate that the electrostatic screening from allosterically bound cations can affect the key residues at the catalytic site and active-site gorge, including E199. Furthermore, an increase in ion concentration can lead to lower reactivity, especially for Li+ ions, which exhibit more cation-hAChE contacts than Na+ and K+. The selective ion binding and their preferred modulation on hAChE are highly related to ion species. This work provides a molecular perspective on selective modulation by different ion species of the enzyme catalytic processes.

Dysregulated Serum Cytokine Production in Pediatric Patients with ß-Thalassemia Major.

ß-Thalassemia major (ß-TM) is an inherited disorder of hemoglobin (Hb) production, which can cause severe anemia. A compromised immune system has been observed in patients with ß-TM, whereas cytokines have a major role in immune modulation. Interleukin-4 (IL-4), IL-8, IL-13 and transforming growth factor-ß (TGF-ß) are critical in initiating pro-inflammatory responses, and the serum levels of those cytokines may be involved in the pathophysiology of ß-thalassemia (ß-thal). To assess this hypothesis, we studied 23 pediatric patients with ß-TM by measuring serum levels of IL-4, IL-8, IL-13 and TGF-ß, as well as evaluating infection frequency per year, total number of transfusions and serum ferritin (SF) levels, together with age-matched healthy controls. We found that patients with ß-thal had higher IL-8, IL-13 and TGF-ß concentrations than normal controls, whereas markedly decreased serum IL-4 level was documented in patients with ß-TM. Serum IL-4 level of ß-thal patients showed a negative significant correlation with infection frequency, total number of transfusions and SF levels. On the contrary, serum levels of IL-8, IL-13 and TGF-ß exerted a positive relationship with those clinical parameters. Taken together, our study implies that dysregulated cytokine profile might contribute to iron overloads and impair immune cell functions, thus serving as useful biomarkers for diagnosis and evaluation of ß-TM in the future. Our study sheds new light on the pathogenesis of ß-TM.

Induction and Monitoring of DNA Phase Separation in Living Cells by a Light-Switching Ruthenium Complex.

Phase separation of DNA is involved in chromatin packing for the regulation of gene transcription. Visualization and manipulation of DNA phase separation in living cells present great challenges. Herein, we present a Ru(II) complex (Ru1) with high DNA binding affinity and DNA "light-switch" behavior that can induce and monitor DNA phase separation both in vitro and in living cells. Molecular dynamics simulations indicate that the two phen-PPh3 ligands with positively charged lipophilic triphenylphosphine substituents and flexible long alkyl chains in Ru1 play essential roles in the formation of multivalent binding forces between DNA molecules to induce DNA phase separation. Importantly, the unique environmental sensitive emission property of Ru1 enables direct visualization of the dynamic process of DNA phase separation in living cells by two-photon phosphorescent lifetime imaging. Moreover, Ru1 can change the gene expression pattern by modulating chromatin accessibility as demonstrated by integrating RNA-sequencing and transposase-accessible chromatin with high-throughput sequencing. In all, we present here the first small-molecule-based tracer and modulator of DNA phase separation in living cells and elucidate its impact on the chromatin state and transcriptome.

Structural, Mechanistic, and Functional Insights into an Arthrobacter nicotinovorans Molybdenum Hydroxylase Involved in Nicotine Degradation.

Arthrobacter nicotinovorans decomposes nicotine through the pyridine pathway. 6-hydroxypseudooxynicotine 2-oxidoreductase (also named ketone dehydrogenase, Kdh) is an important enzyme in nicotine degradation pathway of A. nicotinovorans, and is responsible for the second hydroxylation of nicotine. Kdh belongs to the molybdenum hydroxylase family, and catalyzes the oxidation of 6-hydroxy-pseudooxynicotine (6-HPON) to 2,6-dihydroxy-pseudooxynicotine (2,6-DHPON). We determined the crystal structure of the Kdh holoenzyme from A. nicotinovorans, with its three subunits KdhL, KdhM, and KdhS, and their associated cofactors molybdopterin cytosine dinucleotide (MCD), two iron-sulfur clusters (Fe2S2), and flavin adenine dinucleotide (FAD), respectively. In addition, we obtained a structural model of the substrate 6-HPON-bound Kdh through molecular docking, and performed molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations to unveil the catalytic mechanism of Kdh. The residues Glu345, Try551, and Glu748 of KdhL were found to participate in substrate binding, and Phe269 and Arg383 of KdhL were found to contribute to stabilize the MCD conformation. Furthermore, site-directed mutagenesis and enzymatic activity assays were performed to support our structural and computational results, which also revealed a trend of increasing catalytic efficiency with the increase in the buffer pH. Lastly, our electrochemical results demonstrated electron transfer among the various cofactors of Kdh. Therefore, our work provides a comprehensive structural, mechanistic, and functional study on the molybdenum hydroxylase Kdh in the nicotine degradation pathway of A. nicotinovorans.

[Reproductive characteristics and habitat factors of Acanthopanax giraldii].

The growth parameters,clonal propagation parameters and sexual reproduction parameters of Acanthopanax giraldii population were systematically investigated and analyzed by means of population ecology in this study. The correlation among the above mentioned parameters and the correlation among canopy density,topography and soil fertility factors were analyzed. It is clear that there was a significant correlation among the clonal ramets,the fruit production capacity of the cluster and the new shoot production capacity of the A. giraldii. Sexual reproduction and clonal reproduction played an important role in the continuation of the population. Illumination was the key ecological factor that determined growth type. The increase in canopy density changed the population from " group clonal growth" to " guerrilla clonal growth",and the higher stand closure degree and low-strength herb layer competition was a necessary condition for seed germination and colonization. Under the background of natural forest protection and sustainable development of resources,the reproductive characteristics of wild A. giraldii resulted in the decrease of its recoverable quantity.

An Outbreak of Surgical Site Infections in A Neurosurgical Ward.

Objective To survey an outbreak of surgical site infections in a neurosurgery ward of a tertiary hospital. Methods The patients of surgical site infection were investigated individually based on a uniformly designed epidemiological survey form. The distribution of cases was analyzed by characteristic epidemiology,and a case-control study was carried to explore the risk factors. Results A total of 9 patients with surgical site infections from February 5 to March 7,2014 were identified in 68 patients who had received surgery in a neurosurgery ward,yielding a prevalence of 13.24%. The infections occurred in 7 of 14 patients who had used surgicel,a hemostatic agent,and in 2 of 54 patients who had not used surgicel. (χ2=16.637,P<0.001). Conclusion The use of surgicel may be the cause of this surgical site infection outbreak.

Diastereo-divergent synthesis of chiral hindered ethers via a synergistic calcium(II)/gold(I) catalyzed cascade hydration/1,4-addition reaction.

Hindered ethers are ubiquitous in natural products and bioactive molecules. However, developing an efficient method for the stereocontrolled synthesis of all stereoisomers of chiral hindered ethers is highly desirable but challenging. Here we show a strategy that utilizes in situ-generated water as a nucleophile in an asymmetric cascade reaction involving two highly reactive intermediates, 3-furyl methyl cations and ortho-quinone methides (o-QMs), to synthesize chiral hindered ethers. The Ca(II)/Au(I) synergistic catalytic system enables the control of diastereoselectivity and enantioselectivity by selecting suitable chiral phosphine ligands in this cascade hydration/1,4-addition reaction, affording all four stereoisomers of a diverse range of chiral tetra-aryl substituted ethers with high diastereoselectivities (up to >20/1) and enantioselectivities (up to 95% ee). This work provides an example of chiral Ca(II)/Au(I) bimetallic catalytic system controlling two stereogenic centers via a cascade reaction in a single operation.

Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a ß-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.

[The effect of nicotinamide N-methytransferase overexpression on biological behaviors of SMMC7721 hepatocellar carcinoma cell line].

OBJECTIVE: To study the effect of over expressed nicotinamide N-methytransferase (NNMT) on the malignant biological behaviors of hepatocellular carcinoma cell line SMMC7721. METHODS: The cells transfected with SMMC/NNMT abbreviated as S/NNMT, parental cells including the negative control which transfected with SMMC/pcDNA3. 1 abbreviated as S/P and parental group which abbreviated S. MTT assay and Plate Clone Formation Assay, cell adhension assay and invasion assay were applied to evaluate the effect of NNMT overexpression on the malignant biological behaviors of hepatocellular carcinoma cell line SMMC7721. RESULTS: Compared with the negative control and parental group, MTT assay and Plate Clone Formation Assay demonstrated that over expression of NNMT in SMMC7721 cells could not influence the proliferation clone formation of SMMC7721 cells (P > 0.05). Over expression of NNMT in SMMC7721 cells significantly enhanced the ability of invasion and adhension (P < 0.001). CONCLUSION: NNMT gene can partially influence the malignant behaviors of hepatocellular carcinoma cellline SMMC7721 and increased the ability of invasion and adhension.

Quantum Mechanical/Molecular Mechanical Elucidation of the Catalytic Mechanism of Leukotriene A4 Hydrolase as an Epoxidase.

Leukotriene A4 hydrolase (LTA4H) functions as a mono-zinc bifunctional enzyme with aminopeptidase and epoxidase activities. While the aminopeptidase mechanism is well understood, the epoxidase mechanism remains less clear. In continuation of our prior research, we undertook an in-depth exploration of the LTA4H catalytic role as an epoxidase, employing a combined SCC-DFTB/CHARMM method. In the current work, we found that the conversion of LTA4 to leukotriene B4 (LTB4) involves three successive steps: epoxy ring opening (RO), nucleophilic attack (NA), and proton transfer (PT) reactions at the epoxy oxygen atom. Among these steps, the RO and NA stages constitute the potential rate-limiting step within the entire epoxidase mechanism. Notably, the NA step implicates D375 as the general base catalyst, while the PT step engages protonated E271 as the general acid catalyst. Additionally, we delved into the mechanism behind the formation of the isomer product, Δ6-trans-Δ8-cis-LTB4. Our findings debunked the feasibility of a direct LTB4 to iso-LTB4 conversion. Instead, we highlight the possibility of isomerization from LTA4 to its isomeric conjugate (iso-LTA4), showing comparable energy barriers of 5.1 and 5.5 kcal/mol in aqueous and enzymatic environments, respectively. The ensuing dynamics of iso-LTA4 hydrolysis subsequently yield iso-LTB4 via a mechanism akin to LTA4 hydrolysis, albeit with a heightened barrier. Our computations firmly support the notion that substrate isomerization exclusively takes place prior to or during the initial substrate-binding phase, while LTA4 remains the dominant conformer. Notably, our simulations suggest that irrespective of the active site's constrained L-shape, isomerization from LTA4 to its isomeric conjugate remains plausible. The mechanistic insights garnered from our simulations furnish a valuable understanding of LTA4H's role as an epoxidase, thereby facilitating potential advancements in inhibitor design.

Alterations in the balance of sex hormones may affect rat prostatic inflammation and fibrosis, and osteopontin might be involved in this process.

OBJECTIVE: This study aimed to investigate the effects of sex hormone imbalance on rat prostatic inflammation and fibrosis and identify the key molecules involved. METHODS: Castrated Sprague-Dawley (SD) rats were treated with a constant dose of oestradiol (E2) and different doses of dihydrotestosterone (DHT) to achieve different oestrogen/androgen ratios. After 8 weeks, serum E2 and DHT concentrations, relative seminal vesicle weights, histopathological changes and inflammation were measured, collagen fiber content and oestrogen receptor (ER) and androgen receptor (AR) expression were detected, mRNA sequencing and bioinformatics analysis were performed to identify differentially expressed genes (DEGs). RESULTS: The severity of inflammation in the rat dorsolateral prostate (DLP) was higher, collagen fibre content and ER expression in the rat DLP and prostatic urethra were increased and AR expression in the rat DLP was decreased in the 1:1 E2/DHT-treated group than that in the 1:10 E2/DHT-treated group. RNA-seq analysis identified 487 DEGs, and striking increases in the expression of mRNAs encoding collagen, collagen synthesis and degradation enzymes, growth factors and binding proteins, cytokines and chemokines, and cell-surface molecules were confirmed in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group. mRNA expression of secreted phosphoprotein 1 (Spp1) and protein expression of osteopontin (OPN, encoded by Spp1) were increased in the 1:1 E2/DHT-treated group compared to the 1:10 E2/DHT-treated group, and Spp1 expression correlated positively with Mmp7, Cxcl6 and Igfn1 expression. CONCLUSIONS: The imbalance in the oestrogen/androgen ratio may affect rat prostatic inflammation and fibrosis, and OPN might be involved in this process.

The Symptoms of Benign Prostatic Hyperplasia Patients with Stromal-Dominated Hyperplasia Nodules May Be Associated with Prostate Fibrosis.

Objective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules. Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis. Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis. Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules.

Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPARα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC). AIM OF THE STUDY: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization. MATERIALS AND METHODS: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPARα pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model. RESULTS: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPARα pathway but suppressed NF-κB pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4. CONCLUSIONS: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPARα pathway.

VCC-1 over-expression inhibits cisplatin-induced apoptosis in HepG2 cells.

Vascular endothelial growth factor-correlated chemokine 1 (VCC-1), a recently described chemokine, is hypothesized to be associated with carcinogenesis. However, the molecular mechanisms by which aberrant VCC-1 expression determines poor outcomes of cancers are unknown. In this study, we found that VCC-1 was highly expressed in hepatocellular carcinoma (HCC) tissue. It was also associated with proliferation of HepG2 cells, and inhibition of cisplatin-induced apoptosis of HepG2 cells. Conversely, down-regulation of VCC-1 in HepG2 cells increased cisplatin-induced apoptosis of HepG2 cells. In summary, these results suggest that VCC-1 is involved in cisplatin-induced apoptosis of HepG2 cells, and also provides some evidence for VCC-1 as a potential cellular target for chemotherapy.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier.

BACKGROUND: The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PURPOSE: The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. METHODS: The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. RESULTS: HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. CONCLUSIONS: These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.

Risk factors of Helicobacter pylori infection among adults in northern China.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is one of the leading causes of gastritis, gastric ulcer, gastric cancer and other gastrointestinal diseases. In this study we aim to evaluate those factors that involved in the prevalence of H. pylori infection, such as socioeconomic living conditions, socioeconomic level, eating habits, and H. pylori gene subtype. METHODOLOGY: Included in this study are data on the daily habits and chronic disease history obtained from personal interviews of 798 healthy adults. The presence ofH. pylori infection is identified using an ELISA kit for detection of H. pylori IgG antibodies in serum. H. pylori gene subtype is determined by polymerase chain reaction (PCR) and specific probes. RESULTS: H. pylori prevalence is 54.5% in Northern China and diabetes, hyperlipidemia and atherosclerosis, age and waist circumference played important roles in H. pylori prevalence. VacA-positive strains are the most popular genotype. The most common strain of H. pylori is vacuolating cytotoxin gene A product (VacA), VacA-sla-m2 subtype. CONCLUSIONS: These data support that personal and environmental conditions affect H. pylori infection in adults, and H. pylori gene subtype may play important role in the prevalence of its infection.

The Positive Effect of Perceived Exercise Benefit and the Negative Effect of Perceived Severity of Disease and Weakness on College Students' Amount of Exercise: The Mediate and Suppressor Role of Physical Fitness Evaluation Self-Efficacy.

Background: The decline in the physical fitness of college students has become a serious social problem worldwide. Therefore, exploring the factors affecting the amount of exercise of college students is of great significance in improving college students' physique. According to the expectation value theory and previous studies, perceived exercise benefit and perceived severity of disease and weakness may have positive or negative impact on exercise behavior, and according to the self-efficacy theory, physical evaluation self-efficacy may be the most powerful motivational factors and it play a mediating role between other factors and exercise behavior. Therefore, this study was designed to determine the critical role of physical evaluation self-efficacy in the path of perceived exercise benefit and perceived severity of disease and weakness affecting the amount of exercise of college students. Methods: By means of Physical Fitness Health Belief of College Students Scale and Physical Activity Rating Scale (PARS-3), 801 undergraduate students were investigated in this study. Results: (1) When perceived exercise benefit, exercise self-efficacy, and severity of perceived disease and weakness predicted the amount of exercise separately, the first two have a positive effect on the amount of exercise, but the latter has no effect. However, when these three factors entered the regression equation at the same time, the perceived severity of disease and weakness had a negative effect on the amount of exercise. (2) The influence of physical evaluation self-efficacy on the college students' the amount of exercise was bigger than benefit of perceived exercise and the perceived severity of disease and weakness in both separated and simultaneous comparison conditions. (3) Physical evaluation self-efficacy completely mediated the positive effect of perceived exercise benefits on the amount of exercise and inhibited the negative effect of perceived severity of disease and weakness on the amount of exercise. Conclusion: Physical evaluation self-efficacy has a strong predictive power on the amount of exercise of college students. This was reflected in its ability to mediate the impact of expectation of exercise results and in its ability to suppress the adverse effects of concern about illness on exercise.

Familial left cervical neurofibromatosis 1 with scoliosis: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder affecting many parts of the body with café au lait spots, skeletal deformity, and scoliosis. A familial case of NF1 with scoliosis and a painless mass had not yet been reported. CASE SUMMARY: We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis. His right shoulder was about 5 cm lower than the left, the left side of his face was deformed, and the left submandibular skin was relaxed. The folding and drooping were obvious and movement was poor. Computed tomography revealed the involvement of the neck, upper chest wall, and surrounding left shoulder, accompanied by bone changes and scoliosis. Histological evaluation showed subepidermal pale blue mucoid degeneration, fibrous fusiform cells in the dermis in a fascicular, woven arrangement. His mother had the same medical history. The diagnosis was neurofibromatosis of the left neck. Various parts of the tumor tissue were serially resected during several visits. Eight months after surgery, there was a slight tendency to regrow. CONCLUSION: This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient's growth and development.

[Relationship between IKZF3 Gene Single Nucleotide Polymorphisms and Childhood Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of IKAROS family Zinc finger 3 (IKZF3) gene and the risk of acute lymphoblastic leukemia (ALL) in children. METHODS: The peripheral blood samples from 286 children with ALL and 382 healthy children were collected and divided into ALL group and control group, respectively. The genotypes of IKZF3 gene at rs62066988 C > T and rs12946510 C > T were detected by quantitative PCR with TaqMan detection system, and their correlation with ALL was analyzed. RESULTS: The distribution frequencies of CC, CT and TT genotypes at rs62066988 in ALL group were 58.39%, 37.06% and 4.55%, respectively, while those in control group were 69.19%, 27.68% and 3.13%, respectively. The distribution frequencies of CC, CT and TT genotypes at rs12946510 in ALL group were 58.16%, 34.75% and 7.09%, respectively, while those in control group were 55.76%, 37.43% and 6.81%, respectively. Compared with the control group, the distribution frequency of CT/TT genotype at rs62066988 was significantly increased in the ALL group (OR=1.59, 95%CI: 1.16-2.19, P=0.004). However, there was no significant difference in the distribution of rs12946510 C > T polymorphism between ALL group and control group. CONCLUSION: The CT/TT genotype of IKZF3 at the site of rs62066988 is associated with the increased risk of ALL in children.

Effects of Huangqin Decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. OBJECTIVE: To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). METHODS: The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H-C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. RESULTS: The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H-C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. CONCLUSIONS: HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.