ObjectiveTranscription factor NFE2 was observed abnormal expression in myeloproliferative neoplasm (MPN) patients. However, how NFE2 is transcriptionally regulated remains ambiguous. This study aims to explore the elements and molecular mechanisms involved in the transcriptional regulation of NFE2. MethodsActive enhancers were predicted by public NGS data and conformed experimentally via dual luciferase reporter assay. After that, PRO-seq and GRO-seq data was used to detect enhancer RNAs transcribed from these enhancers. RACE was utilized to clone the full length enhancer RNA (eRNA) transcripts, and RT-qPCR was used to measure their expression in different leukemia cell lines as well as the transcript levels during induced differentiation. Finally, to investigate the molecular function of the eRNA, overexpression and knockdown of the eRNA via lentivirus system was performed in K562 cells. ResultsWe identified three enhancers regulating NFE2 transcription, which located at -3.6k, -6.2k and +6.3k from NFE2 transcription start site (TSS) respectively. At the -3.6k enhancer, we cloned an eRNA transcript and characterized that as a lncRNA which was expressed and located in the nucleus in three types of leukemia cell lines. When this lncRNA was overexpressed, expression of NFE2 was upregulated and decreases of K562 cell proliferation and migration ability were observed. While knocking down of this lncRNA, the level of NFE2 decreases correspondingly and the proliferation ability of K562 cells increases accordingly. ConclusionWe identified an enhancer lncRNA that regulates NFE2 transcription positively and suppresses K562 cell proliferation.

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

OBJECTIVE: To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea. METHODS: Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints. RESULTS: Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05). CONCLUSION In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.
Humans ; Female ; Microcirculation ; Dysmenorrhea/therapy* ; Menstrual Cycle ; Acupuncture Points ; Acupuncture Therapy

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Surgery remains the primary and most successful therapy option for the treatment of early- and mid-stage HCCs, but the high heterogeneity of HCC renders prognostic prediction challenging. The construction of relevant prognostic models helps to stratify the prognosis of surgically treated patients and guide personalized clinical decision-making, thereby improving patient survival rates. Currently, the prognostic assessment of HCC is based on several commonly used staging systems, such as Tumor-Node-Metastasis (TNM), Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC). Given the insufficiency of these staging systems and the aim to improve the accuracy of prognostic prediction, researchers have incorporated further prognostic factors, such as microvascular infiltration, and proposed some new prognostic models for HCC. To provide insights into the prospects of clinical oncology research, this review describes the commonly used HCC staging systems and new models proposed in recent years.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Prognosis ; Neoplasm Staging ; Survival Rate ; Retrospective Studies

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95％CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95％CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95％CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95％CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95％CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95％CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95％CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine

ObjectiveQuorum-sensing (QS) and small regulatory RNA (sRNA) play key regulatory roles in many signaling cascades of Pseudomonas aeruginosa. To investigate whether sRNA is involved in P. aeruginosa QS system, screening QS system-related sRNA, and to construct sRNA overexpression and deletion strains of Pseudomonas aeruginosa for further study of sRNA function.MethodsSRNA associated with the QS system was screened by qPCR and RNA-sequencing (RNA-seq). The target gene were amplified by PCR and inserted into the overexpression vector pROp200 or the homologous recombination vector pGSM-MR, respectively. The connection reaction solution of pROp200-sRNA and pGSM-ΔsRNA was transformed into Escherichia coli DH5a and SM10lp, respectively. The recombinant vectors were identified by PCR. The pROp200-sRNA was transformed into PAO1 by heat shock method, and the pGSM-ΔsRNA was transferred from SM10lp to PAO1 by conjugation. SRNA overexpression and deletion strains were identified by PCR, DNA sequencing and qPCR, the determination of the growth curves and the pyocyanin levels of strains.ResultsFive QS -associated sRNA P26, P5316.1, P30, P34 and AmiL were successfully screened by RNA-seq and qPCR. PCR, DNA sequencing and qPCR showed that sRNA of AmiL, P30 and P34 overexpression and knockout were successful. Compared with wild-type strain, sRNA overexpression and knockout had no significant effect on bacterial growth curve. It were notably that overexpression of AmiL and P30 inhibited and increase the production of pyocyanin, respectively (P<0.01), while deficiency of AmiL and P30 in the genome resulted in significantly increase and decrease of pyocyanin, respectively (P<0.01). Overexpression and deletion of P34 had no significant effect on pyocyanin synthesis (P>0.05).ConclusionThe sRNA overexpression and deletion strains have been successfully constructed and can be used to study the regulatory relationship between sRNA and QS systems, and to further functional study.

Objective:To analyze the pathogenesis and clinical characteristics of appendiceal neoplasms and its prognosis.Methods:In recent 14 years, 94 appendiceal neoplasms were found among 6 334 patients undergoing appendectomy in a single center of Ordos Central Hospital.The initial symptoms, clinical features, auxiliary examinations, pathology, surgical methods, and clinical outcomes of 94 patients diagnosed with appendix tumors were recorded.Results:Appendiceal neoplasms accounted for 1.48% for all undergoing appendectomy. Among these 94 cases, 49 cases were female and 45 cases were male. The median age was 59.5 years. 80 cases were followed up with a follow-up rate of 85.1%, and the follow-up period was 2-175 months.The 5-year overall survival rate was 91.9% and the 10-year overall survival rate was 88.9%.The results of univariate analysis of prognosis showed that the prognosis of patients with WBC count>10.0×10 9/L (χ 2 =8.884, P=0.003) and lymph node metastasis(χ 2 =17.216, P=0.001) was relatively poor. The prognosis of appendiceal adenocarcinoma is relatively poor compared with mucinous tumors(χ 2=13.857 , P=0.001 ). Conclusions:The incidence of appendiceal neoplasms is very low; Chronic lower right abdominal pain accounted for a large proportion of the manifestations; Classification of appendiceal neoplasms, leukocyte count and lymph node metastasis predict the prognosis of patients with appendiceal neoplasms.

Background: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferatoractivated receptor γ (PPARγ) expression with GDM in overweight or obese women. Methods: One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting. Results: The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ± 7.87 ng/mL vs. 25.85 ± 7.29 ng/mL, G2 vs. N2: 17.06 ± 6.74 ng/mL vs. 21.62 ± 7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM+ overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05). Conclusions Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

Objective: To investigate the incidence of human rhinovirus (HRV) infection in hospitalized patients in emergency department. Methods: A total of 94 emergency patients admitted to the emergency department from November to December of 2018 were enrolled in this study. The rhinovirus infection and related risk factors were analyzed. Results: HRV infection occurred in 17 out of 94 hospitalized patients in emergency department, the infection rate was 18.09%; Multiple HRV serotypes were prevalent from November to December of 2018, which were A9, A10, A16, A31, A73, B42 and C3. Elderly patients are at high risk of rhinovirus infection; Rhinovirus infection may increase the course of inpatients. Conclusions From November to December of 2018, multiple serotypes of HRV infections in the emergency department of Bengbu, Anhui, and HRV easily infected elderly inpatients.