Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective:To discover the relationship between the RNF213 gene and acute myeloid leukemia(AML),and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells.Methods:Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database.Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022.RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein.Perform survival of patients was analysed by Kaplan-Meier.Meanwhile,the expression levels of RNF213 mRNA and protein were detected in AML cell lines(THP-1,OCI-AML2).CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells;flow cytometry was used to detect apoptosis rate of cell.CCK-8 and colony formation assay were used to detect cell proliferation.Western blot was used to detect the expression level of Cleaved-Caspase 3 protein.Results:Compared with the control group,the expression level of RNF213 in AML patients was significantly increased,and patients with high expression of RNF213 have a worse prgnosis.Higher expression level of RNF213 protein in THP-1 cells.After knocking down the RNF213 gene of THP-1 cells,cell proliferation was significantly reduced,and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased.Conclusion:AML patients have high expression of RNF213,and the prognosis of high expression patients is poor.The RNF213 gene affects AML cell proliferation and apoptosis,and may be a prognostic marker and potential therapeutic target for AML.

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.
Child, Preschool ; Exchange Transfusion, Whole Blood/adverse effects* ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant ; Infant, Newborn ; Kernicterus/therapy* ; Phototherapy/methods* ; Retrospective Studies

Objective: To explore the association between self-reported gingival bleeding and prevalent hypertension among adults in Zhejiang with a cross-sectional study. Methods: After excluding participants with self-reported, physician-diagnosed heart diseases, stroke, diabetes, cancer, and those who never or rarely brush their teeth at baseline study, 48 625 participants aged 30-79 in the China Kadoorie Biobank (CKB) study from Tongxiang, Zhejiang were included for the final analysis. Three multivariable logistic regression models were used to estimate the odds ratios (ORs) for the associations of self-reported gingival bleeding with prevalent hypertension. Results: The mean age of women was (51.2±9.2) years, and 42.9% of participants had prevalent hypertension. The percentage of self-reported frequent gingival bleeding was 6.56% (95%CI: 6.38%-6.75%), significantly higher among women (8.08%, 95%CI: 7.82%-8.35%) than among men (4.36%, 95%CI: 4.12%-4.60%) (P<0.001). After adjusting for socio-demographic factors, behavioral lifestyle, sleep duration, BMI, waist circumference, snoring, in comparison with men whose gingivae never or rarely bleed while brushing teeth, the odds ratio (95%CI) of hypertension for those with occasional, and frequent gingival bleeding were 1.04 (0.96-1.12) and 1.18 (1.02-1.37), respectively (trend P =0.038). The corresponding figures for women were 0.96 (0.91-1.02) and 0.95 (0.86-1.05), respectively (trend P=0.344). Conclusion: Frequent gingival bleeding was positively associated with prevalent hypertension among men.
Adult ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Gingival Hemorrhage ; Humans ; Hypertension/epidemiology* ; Male ; Middle Aged ; Risk Factors ; Self Report

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

This study aimed to clarify the microbial diversity, dominant species and the change of community structures in the fermentation of Liushenqu(Massa Medicata Fermentata), and explore the material foundation of its pharmacodynamics effect. On the basis of standardizing the fermentation process, Massa Medicata Fermentata was prepared by screening and optimizing the recipes and the standard formula issued by the Ministry. The community structure and growth process of fungi and bacteria in the samples at five time points(0, 17, 41, 48, 65 h) in the fermentation process of Massa Medicata Fermentata were analyzed by using isolation and culture of eight different media and high-throughput DNA sequencing technology. The results indicated that the samples of the two recipes pre-sented high microbial diversity at the initial fermentation stage, with Aspergillus spp. as the dominant species. As the fermentation process goes forward, Saccharomycopsis fibuligera and Rhizopus oryzae soon became dominant species from 17 h after fermentation commencement point to the fermentation end, while the other species were inhibited at a lower level from 17 h. The species diversity of bacteria in the initial fermentation samples was also high, and Enterobacter was the dominant species. Enterobacter cloacae, Pediococcus pentosaceus and Cronobacter sakazakii became dominant bacterial species 17 h after fermentation commencement, while the species diversity was decreased. Our results will be a scientific basis for promoting the fermentation process of Massa Medicata Fermentata by using pure microbial cultures.
Drugs, Chinese Herbal ; Fermentation ; Fungi/genetics* ; Microbiota ; Saccharomycopsis

Following small molecules and monoclonal antibodies, oligonucleotides are expected to overcome the rare and refractory human diseases. It has been attracted the attention of the pharmaceutical industry since the approval of six oligonucleotides in recent years because of their unique mechanism of regulating disease gene transcription at the RNA level. As a new class of drug molecules, oligonucleotides are highly polar, charged, and need to be improved by means of chemical modification and drug delivery systems. And therefore, they have different clinical pharmacology properties compared with chemical molecules and monoclonal antibodies, which pose new challenges for early clinical development. This paper reviews the characteristics of oligonucleotides from the perspective of technological development, mechanism of action, human pharmacokinetics, efficacy and safety.

Objective: To compare the results obtained from the computer-aided sperm analysis (CASA) systems of the two fully-automated commercial sperm quality analyzers, Hamilton-Thorn IVOS Ⅱ (IVOS Ⅱ) and Spanish Sperm Class Analyzer (SCA). METHODS: A total of 99 semen samples were collected in the Center of Reproduction of Shenzhen Zhongshan Urology Hospital from September 2018 to October 2018 and, according to the sperm concentration, divided into groups A (<15 ×10⁶/ml), B (15－50 ×10⁶/ml) and C (>50 ×10⁶/ml). IVOS Ⅱ, SCA and manual microscopy were used for the examination of each sample, followed by comparison of the sperm concentration, sperm motility and percentage of progressively motile sperm (PMS) obtained from IVOS Ⅱ and SCA. RESULTS: The sperm concentrations derived from IVOS Ⅱ and SCA were significantly higher than that from manual microscopy in group A (［10.24 ± 4.60］ and ［10.20 ± 5.11］ vs ［8.45 ± 4.15］ ×10⁶/ml, P < 0.05), but showed no statistically significant difference in group B (［30.95 ± 11.84］ and ［31.81 ± 12.90］ vs ［29.14 ± 10.65］ ×10⁶/ml, P > 0.05) or C (［102.14 ± 45.97］ and ［109.48 ± 46.32］ vs ［104.74 ± 41.87］ ×10⁶/ml, P > 0.05). Significant differences were not observed between IVOS Ⅱ and SCA in the percentage of PMS (［24.21 ± 14.62］% vs ［23.92 ± 15.42］%, P > 0.05) or sperm motility (［37.48 ± 19.34］% vs ［37.69 ± 16.61］%, P > 0.05) in group B, nor in group C (PMS: ［30.80 ± 12.06］% vs ［32.98 ± 16.10］%, P > 0.05; sperm motility: ［44.50 ± 15.62］% vs ［47.26 ± 17.46］%, P > 0.05). Both the percentage of PMS and sperm motility obtained from IVOS Ⅱ were remarkably lower than those derived from SCA in group A (PMS: ［18.54 ± 12.96］% vs ［22.90 ± 12.88］%, P < 0.05; sperm motility: ［26.97 ± 14.05］% vs ［34.90 ± 15.18］%, P < 0.05). IVOS Ⅱ and SCA both showed a high repeatability (CV <15%), and the former exhibited an even higher one than the latter, in detection of sperm concentration, sperm motility and the percentage of PMS. CONCLUSIONS IVOS Ⅱ and SCA both had a good consistency in the results of sperm concentration, motility and progressive motility, but showed a poor comparability with low-concentration semen samples.

PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.
Diagnosis ; Epidemiology* ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Methods ; Nasopharyngeal Neoplasms ; Prognosis ; Proportional Hazards Models ; SEER Program ; Survival Rate