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.

The article analyzes chief physician SUN Wuquan's empirical characteristics in treating neck-type cervical spondylosis:disease differentiation combined with pattern differentiation,emphasizing the assessment of tendons and bones,with DING's Tuina(Chinese therapeutic massage)manipulations and static Gongfa(Qigong exercise)as the predominant treatment,inherits the academic features of DING's Tuina school,"paying equal attention to tendons and bones,putting function first";thus provides a reference for treating neck-type cervical spondylosis with Tuina therapy.

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

OBJECTIVE: To report an overview of bariatric & metabolic surgery performed in 2018 in North China. METHODS: Based on prospective and observational North China Bariatric & Metabolic Surgery Clinical Database(NC-BMD), the study of evaluating the number and the type of bariatric &metabolic surgery procedures was performed in North China. Demographic characteristic, obesityrelated diseases and operational information were also analyzed. RESULTS: In 2018, 17 centers from 7 regions in North China contributed a total of 728 registration data. Valid data were analyzed from 16 centers. The patients' median (minimum, maximum) BMI pre-surgery was 38.4(24.7,95.2). The overall proportion of female patients was 74.7%, and mean±SD age was(32.5±8.29) years, while male patients was 25.3%, and mean±SD age was (32.7±9.90) years. According the data 93.9% laparoscopic sleeve gastrectomy(LSG), 4.4% laparoscopic Roux-en-Y gastric bypass (LRYGB) and 1.7% other operation types. 29.2% of patients had a history of type 2 diabetes, 69.4% had sleep apnea, and 22.6% had polycystic ovary syndrome before operation. CONCLUSION: The establishment of NC-BMD has laid a solid foundation for data registration in North China. Based on current data, LSG is the mainstream of bariatric and metabolic surgery in North China this year.

Cells, Cultured ; Cyclic Nucleotide Phosphodiesterases, Type 2 ; antagonists & inhibitors ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Glucosides ; pharmacology ; Humans ; Lung ; cytology ; embryology ; Phenols ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVE: To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD). METHODS: Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42 (Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice. RESULTS: Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01) in APP/PS1 mice. CONCLUSION Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. METHODS: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. RESULTS: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly. CONCLUSION Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Interleukin-1beta ; metabolism ; Pharyngitis ; drug therapy ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

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 clinical application of modified electroconvulsive therapy (MECT),and provide the references for more standardized and rational use of MECT.Methods A retrospective study was performed by stratified random sampling method.The clinical data of 1 330 psychiatric inpatients from January 2006 to December 2015 in Henan Psychiatric Hospital were analyzed retrospectively,and the clinical application of MECT was investigated,including the proportion of psychiatric inpatients receiving MECT,the situation of combined use of MECT and antipsychotic drugs,and the routine examination results before and after MECT.Results The proportion of receiving MECT in schizophrenic patients was the highest,it is 11.36％ (81/713),the second was depressive episode (5.61％,12/214),followed by dissociative conversion disorder (5.56％,2/36),bipolar disorder (5.34％,7/131),organic mental disorder (3.23 ％,1/31) and other mental disorders (2.93％,6/205).There were significant differences in the distribution of various mental disorders between the non electroshock group and the electroshock group (x2 =21.728,P ＜ 0.05).The proportion of the patients without electric shock and the patients with single drug,two drugs,triple therapy or quadruple therapy was 0.92％,17.43 ％,56.88％,21.10％ and 3.67％,respectively.The proportion of the patients with two or more antipsychotic drugs was 81.65％ in the electroshock group.The antipsychotics were olanzapine (28.44％),clozapine (27.52％),quetiapine (26.61％) and risperidone (24.77 ％) according to the drugs used frequently in the electroshock group.The results of routine blood test were compared among the time points of before treatment,the 1st,2nd,3 rd week of MECT and 1 week after MECT in the shock group,which showed that there was significant difference in white blood cell count (F =2.570,P ＜ 0.05);but there was no significant difference in the levels of platelet,hemoglobin and red blood cell (P ＞ 0.05);the level of white blood cell returned to normal within two weeks in 93.33％ patients with increased white blood count.The myocardial enzymes and liver function tests were not perfect during the treatment of MECT and after treatment.There was no long-term systematic evaluation of cognitive function and quality of life in patients with electroconvulsive shock.Conclusions The probability of using MECT in the patients with schizophrenia is more than that in the patients with depression.MECT is used in combination with two or more antipsychotic drugs.MECT may cause a short increase in white blood cells,but the white blood cell level in most patients can recover to normal levels after symptomatic treatment.The clinical data for treatment and prognosis in patients with MECT are inadequate,so it is necessary to improve the medical record.