The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

OBJECTIVE: To study the clinical characteristics, drug sensitivity of isolated strains, and risk factors of drug resistance in children with invasive pneumococcal disease (IPD). METHODS: The clinical characteristics and drug sensitivity of the isolated strains of 246 hospitalized children with IPD in nine grade A tertiary children's hospitals from January 2016 to June 2018 were analyzed. RESULTS: Of the 246 children with IPD, there were 122 males and 124 females. Their ages ranged from 1 day to 14 years, and among them, 68 (27.6%) patients were less than 1 year old, 54 (22.0%) patients were 1 to 2 years old, 97 (39.4%) patients were 2 to 5 years old, and 27 (11.0%) patients were 5 to 14 years old. Pneumonia with sepsis was the most common infection type (58.5%, 144/246), followed by bloodstream infection without focus (19.9%, 49/246) and meningitis (15.0%, 37/246). Forty-nine (19.9%) patients had underlying diseases, and 160 (65.0%) had various risk factors for drug resistance. The isolated Streptococcus pneumoniae strains were 100% sensitive to vancomycin, linezolid, moxifloxacin, and levofloxacin, 90% sensitive to ertapenem, ofloxacin, and ceftriaxone, but had a low sensitivity to erythromycin (4.2%), clindamycin (7.9%), and tetracycline (6.3%). CONCLUSIONS IPD is more common in children under 5 years old, especially in those under 2 years old. Some children with IPD have underlying diseases, and most of the patients have various risk factors for drug resistance. Pneumonia with sepsis is the most common infection type. The isolated Streptococcus pneumoniae strains are highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin, ertapenem, and ceftriaxone in children with IPD.
Anti-Bacterial Agents ; Ceftriaxone ; Child ; Child, Preschool ; Drug Resistance ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Pneumococcal Infections ; Streptococcus pneumoniae

AIM:To investigate the expression of IFN-γ,IL-4 and IL-17A in asthmatic mice vaccinated with bacillus Calmette-Guérin(BCG)and hepatitis B(HepB)in the neonatal period.METHODS: BALB/c mice were ran-domly divided into BGG+HepB+ovalbumin(OVA)group(B/H/O group),B/O group,H/O group,B/H group,OVA group,BCG group,HepB group and normal saline(NS)group(n=6).The mice in B/H/O group and B/H group at 0, 7 and 14 d received subcutaneous injection of 1×105CFU BCG for 3 times,while at 0 and 28 d received intramuscular in-jection of 1.5 μg HepB on the hindlimb twice.The mice in other groups were individually vaccinated with BCG or HepB. OVA sensitization and aerosol inhalation were performed to establish the asthma model.The lung tissues were collected for HE staining.Bronchoalveolar lavage fluid(BALF)and peripheral blood(PB)were collected,and the number of eosino-phils(EOS)in BALF was counted.The serum levels of IFN-γand IL-4,and the level of IL-17A in lung tissue homoge-nate were measured by ELISA.RESULTS: The pathological changes of the lung in OVA group, B/O group, B/H/O group and H/O group were observed.There were extensive inflammatory cell infiltration around the bronchus,and epithe-lial cell hypertrophy.Those in B/H/O group and H/O group were worse than those in OVA group, while those in B/O group was better than those in OVA group.Total BALF cell counts in B/H/O group,B/O group and H/O group were de-creased(P<0.05)as compared with OVA group.The BALF EOS count in B/H/O group was higher than that in B/H group,that in B/O group was higher than that in BCG group,and that in H/O group was higher than that in HepB groups (P<0.05).Compared with H/O group, OVA group and NS group, the serum IFN-γ/IL-4 ratio in HepB group was in-creased(P<0.05),and compared with B/H/O group,B/O group,OVA group and NS group,that in B/H group was al-so increased(P<0.05).Compared with OVA group, the level of IL-17A in the lung tissues of B/H/O group and B/O group was decreased(P <0.05), and compared with B/O group, that in B/H/O group was further decreased(P <0.05).CONCLUSION:Combined vaccination of BCG and HepB reduces the inflammotory responses in the lung tissues of asthmatic mice.The mechanism may be related with the decrease in the release of IL-4, the increase in IFN-γ/IL-4, and the inhibition of IL-17A expression.

Objective To establish a high performance liquid chromatography (HPLC) through the optimization of the chromatographic conditions, which can detect the contents of clenbuterol hydrochloride (CL) residues in animal edible product in a large quantity. Methods The animal edible product were extracted by perchloric acid, and then impurities were removed by liquid-liquid extraction (LLE) which used ethyl acetate- isopropanol. After the organic phase was concentrated, C18 column (150 mm×4.6 mm, 5 μm) was used to separate CL. Mobile phase were methanol-sodium dihydrogen phosphate, and then determined by HPLC. Results A good linear response was obtained over the range of 0.2-10.0 μg/mL with the correlation coefficient (r) 0.99984. The method determination limit was 0.15 μg/kg which was lower than the National standard method 0.5μg/kg. The retention time of the CL was 6.51 min, the chromatographic peak was good. The recovery rates spiked with standards 1.6-12 μg were 92.86％-100.93％, which was higher than National standard method (89.79％-92.36％) . The precision of intra-day and inter-day were both under 5％, which lower than National standard. Conclusion The optimized chromatographic conditions are suitable for the large quantity determination of clenbuterol hydrochloride in animal edible product.

Objective To investigate the effect on radioactivity in drinking water around Qinshan nuclear power station (QNPS)in normal operational condition.Methods The field monitoring and laboratory analysis methods were adopted to detect the total radioactivity level in drinking water in 2015,according to different distances from the nuclear island and different types of water.Results The total alpha and total beta radioactivity level in drinking water around QNPS were 0.027(0.098)Bq /L and 0.263(0.071)Bq /L respectively,which were obviously lower than the national health standard limits(total alpha and total beta are 0.5,1.0 Bq /L respectively).Total radioactivity level had no relation with the distance from the nuclear island (P >0.05).The total alpha radioactivity in deep well water was the highest among the investigated three types of drinking water,and the highest value was 0.224 Bq /L.The beta radioactivity level in river water was the highest,and the highest value was 0.408 Bq /L.The total alpha radioactivity level was 0.017 (0.013)Bq /L in 2015, higher than the average level during 2010—2014.The beta radioactivity average level was 0.319 (0.102)and 0.289 (0.055)Bq /L,also higher than the average level during 2010—2014.Conclusion The total radioactivity in drinking water among nuclear power plant is in normal background level,so at present there is no effect of the radioactive contamination on drinking water around QNPS in nuclear power plant's normal operational condition.

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.
Animals ; Benzopyrans ; toxicity ; Caesalpinia ; toxicity ; Drugs, Chinese Herbal ; toxicity ; Female ; Indenes ; toxicity ; Male ; Mice ; Mice, Inbred ICR ; Pregnancy ; Reproduction ; drug effects

Objective To analyse the change of hepatic glycogen in the process of hepatocellular carcinoma development in N -nitrosodiethy-lamine(DEN) -induced mice, and investigate the relationship between the hepatic glycogen content and the different stage of liver cancer . Methods There were forty clean and healthy male mice .They were di-vided in two groups ,the normal group ( n=3 ) and the model group ( n=37).After adapting environment in one week ,the group of normal mice were sacrificed and all the model animals were administrated by solution of DEN (30 μg? mL-1 ) in the carcinoma-induced period.Every three mice were sacrificed in the this group induced by DEN in 4 , 8 , 12 , 16 , 20 ,24 weeks(n=21).The obtained liver tissues divided in seven groups and embedded by paraffin were cut at thick piece .After staining with pe-riodic acid-Schiff ( PAS) the hepatic glycogen were observed .In order to obtain the mean optical density , samples of each group were disposed by the software Motic Images Advanced 3.2.Lastly.Analysis of variance ( ANOVA) test was followed by individual comparison by Student -New-man-Keul test using SPSS V16.0.Result The contents of hepatic gly-cogen in normal group , 8-week and 12-week groups were decreased successively and significantly , and the 16-week were least .The con-tents of hepatic glycogen in 16-week compared with 20-week and 24-week groups were increased successively and significantly . Conclusion In the process of development of hepatic carcinoma induced by DEN , the regular of hepatic glycogen′s change was decreasing gradually at the prior period ,and then the level of hepatic glycogen increased later .

This study aimed to assess the reliability of experienced Chinese orthodontists in evaluating treatment outcome and to determine the correlations between three diagnostic information sources. Sixty-nine experienced Chinese orthodontic specialists each evaluated the outcome of orthodontic treatment of 108 Chinese patients. Three different information sources: study casts (SC), lateral cephalometric X-ray images (LX) and facial photographs (PH) were generated at the end of treatment for 108 patients selected randomly from six orthodontic treatment centers throughout China. Six different assessments of treatment outcome were made by each orthodontist using data from the three information sources separately and in combination. Each assessment included both ranking and grading for each patient. The rankings of each of the 69 judges for the 108 patients were correlated with the rankings of each of the other judges yielding 13 873 Spearman rs values, ranging from -0.08 to +0.85. Of these, 90% were greater than 0.4, showing moderate-to-high consistency among the 69 orthodontists. In the combined evaluations, study casts were the most significant predictive component (R(2)=0.86, P<0.000 1), while the inclusion of lateral cephalometric films and facial photographs also contributed to a more comprehensive assessment (R(2)=0.96, P<0.000 1). Grading scores for SC+LX and SC+PH were highly significantly correlated with those for SC+LX+PH (r(SC+LX)vs.(SC+LX+PH)=0.96, r(SC+PH)vs.(SC+LX+PH)=0.97), showing that either SC+LX or SC+PH is an excellent substitute for all three combined assessment.
Adolescent ; Cephalometry ; standards ; China ; Dental Models ; standards ; Esthetics, Dental ; Female ; Humans ; Male ; Malocclusion, Angle Class I ; therapy ; Malocclusion, Angle Class II ; therapy ; Malocclusion, Angle Class III ; therapy ; Orthodontics ; standards ; Peer Review, Health Care ; standards ; Photography ; standards ; Reproducibility of Results ; Treatment Outcome

OBJECTIVETo compare the incidence rates of postoperative urinary incontinence between transurethral bipolar plasmakinetic enucleation and resection of the prostate (PKERP) and transurethral bipolar plasmakinetic resection of the prostate (PKRP), and provide evidence for the clinical application of PKERP.

METHODSTotally, 180 BPH patients were equally and randomly assigned to undergo PKERP and PKRP, respectively. We measured the urinary incontinence of the patients by pad test at 24 hours after extubation and every week after surgery for 4 weeks. Meanwhile, we recorded and compared the PSA level, prostate volume, Qmax, residual urine, IPSS, QOL, and the results of pad test between the two groups before and after surgery.

RESULTSThe incidence rates of urinary incontinence in the PKERP and PKRP groups were 35.56% and 18.89% (P < 0.01) at 24 hours after extubation, 20.00% and 7.78% at 1 week after surgery (P < 0.05), and 3.33% and 2.22% at 2 weeks. There was no significant difference in the severity of urinary incontinence between the two groups at any time point (P > 0.05). No permanent urinary incontinence was observed in either group.

CONCLUSIONCompared with PKRP, PKERP has a higher incidence rate of short-term urinary incontinence in the treatment of BPH, but not that of genuine incontinence, with similar severity and recovery time.

Aged ; Humans ; Incidence ; Male ; Postoperative Complications ; epidemiology ; Prostatic Hyperplasia ; surgery ; Single-Blind Method ; Transurethral Resection of Prostate ; adverse effects ; methods ; Urinary Incontinence ; epidemiology