ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.
Age Factors ; Aged ; COVID-19/therapy* ; China ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Odds Ratio ; Propensity Score ; Retrospective Studies ; Survival Rate

Objective: To clone CDS sequence of Dioscorea opposita SUS gene and analyze the protein structure,in order to provide a theoretical basis for the regulation mechanism of SUS gene and the synthesis mechanism of D.opposita polysaccharides.Method: Total RNA in D.opposita was extracted and reverse-transcribed into first strand of cDNA.Specific primers were designed according to an annotated SUS gene sequence obtained from the laboratory D.opposita genome database,and the coding region of the SUS gene was obtained by gene cloning technique and the protein sequence characteristics were analyzed by protein prediction analysis software.Result: A 2 448 bp gene sequence was cloned with a complete open reading frame (ORF).The gene was named DoSUS1.The formula of protein encoded by DoSUS1 gene in D.opposita was C₄₂₀₉H₆₅₃₄N₁₁₁₅O₁₂₀₅S₂₃,and the molecular weight was 9 788.32,the total number of amino acids was 815,the theory isoelectric point (PI) was 6.10,the extinction coefficient was 110 505,the aliphatic index (AI) was 94.15,the instability index was 32.18,and the grand average of hydropathicity (GRAVY) was-0.225.It was a stable and soluble acidic protein.There were phosphorylation sites in the DoSUS1 amino acid sequence,with no transmembrane region and signal peptide.The secondary structure and the tertiary structure showed that DoSUS1 was an α class protein.Functional domain predictions showed that DoSUS1 had sucrose synthesis domain and glycosyl transfer domain.The homology alignment showed that the amino acid sequence of DoSUS1 was more than 80% similar to the amino acid sequence of the aligned monocots.The phylogenetic tree showed that DoSUS1 was closely related to SUS of monocotyledon evolution.Conclusion: The coding sequence of SUS gene was cloned from D.opposita for the first time,and its protein structure was analyzed to lay a foundation for further studying the roles of SUS in the growth and polysaccharide synthesis of D.opposita.

OBJECTIVES: To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. METHODS: BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. RESULTS: The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). CONCLUSIONS The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.
Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Expression ; drug effects ; Hepatocytes ; drug effects ; metabolism ; Humans ; Liver ; drug effects ; injuries ; metabolism ; Liver Diseases ; drug therapy ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Pharmacology

Objective:To explore the clinical efficacy,safety and tolerability of nasogastric enteral nutrition (NGEN) on moderate-severe acute pancreatitis (M-SAP).Methods:Sixty patients diagnosed as M-SAP and admitted admitted to Department of Gastroenterology,Affiliated Hospital of Southwest Medical University from November 2013 to August 2014 were randomized to receive enteral nutrition (EN) via a nasogasteic tube (n =30) or a nasojejunal tube (n=30).The intestinal permeability (endotoxin,D-lactic acid),inflammation index (CRP、IL-6、TNF-α),nutrition status,nutrition-related adverse effects (reflux aspiration,diarrhea and abdominal pain worse situation),condition assessment (APACHE Ⅱ and MCTSI),and prognosis (infection complications,mortality,length of hospital stay,hospital expenses)were collected and compared.Results:There was no statistically significant difference in the two groups as for intestinal permeability,inflammation index,evaluation of nutritional status,overall condition assessment,and prognosis (P ＞ 0.05).On the reflux aspiration,the rate of nasogastric tube enteral nutrition group (NG group) was 20％,nasojejunal enteral nutrition group (NJ group) was 3.3 ％,the difference was statistically significant (P ＜ 0.05).Conclusion:Either NGEN or NJEN has the similar effects on disease evolution,nutrition condition,intestinal permeability and prognosis of M-SAP.NGEN is simple and worthy of clinical attention.The nasogastric may more easily lead to reflux aspiration than the nasojejunal route.It requires more randomized controlled study to investigate its safety on SAP.

BACKGROUNDThe prevalence of childhood asthma has been increasing in China. This study aimed to compare the prevalence, diagnosis, and treatment of asthmatic children from urban and rural areas in Beijing, China.

METHODSSchools, communities, and kindergartens were randomly selected by cluster random sampling from urban and rural areas in Beijing. Parents were surveyed by the same screening questionnaires. On-the-spot inquiries, physical examinations, medical records, and previous test results were used to diagnose asthmatic children. Information on previous diagnoses, treatments, and control of symptoms was obtained.

RESULTSFrom 7209 children in rural areas and 13,513 children in urban areas who completed screening questionnaires, 587 children were diagnosed as asthma. The prevalence of asthma in rural areas was lower than in urban areas (1.25% vs. 3.68%, χ2 = 100.80, P < 0.001). The diagnosis of asthma in rural areas was lower than in urban areas (48.9% vs. 73.9%, χ2 = 34.6, P < 0.001). Compared with urban asthmatic children (56.5%), only 35.6% of rural asthmatic children received inhaled corticosteroids (P < 0.05). The use of bronchodilators was also lower in rural areas than in urban areas (56.5% vs. 66.4%, χ2 = 14.2, P < 0.01).

CONCLUSIONThe prevalence of asthma in children was lower in rural areas compared with children in the urban area of Beijing. A considerable number of children were not diagnosed and inadequately treated in rural areas.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Asthma ; epidemiology ; Beijing ; epidemiology ; Child ; Child, Preschool ; China ; epidemiology ; Cross-Sectional Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Prevalence ; Surveys and Questionnaires

MISA (MicroSAtelite) software was employed to screen SSRs in 68 787 contigs of Swertia mussotii transcriptome sequences. 5 610 SSRs were distributed in 5 099 contigs which accounted for 7.41% of 68 787 contigs. There are 220 kinds of SSR motifs existing in S. mussotii transcriptome. On average, SSRs occurred every 12.60 kb in length. In the SSRs, the tri-nucleotide repeat motif was the most abundant (45.99%), followed by the di-nucleotide (41.62%). AT/TA and AAT/TTA were the main types of motif in di-, tri-nucleotide repeats. The repeat numbers of SSRs which from S. mussotii transcriptome SSRs were mainly from 5 to 10 and motif length of them mostly ranged from 12 bp to 30 bp. A total of 30 651 contigs were annotated, and only 1 447 SSRs were occurred in protein-coding regions. In the six repeat motifs, tri-nucleotide repeats were the most abundant in coding regions (928). There are abundant SSRs in S. mussotii transcriptome with high frequency and various types, indicating their usefulness in theory. This research may lay the foundation for designing the targeted SSR primers and developing SSR molecular markers by mining the information of SSRs loci in S. mussotii transcriptome sequences data.
Data Mining ; Medicine, Tibetan Traditional ; Microsatellite Repeats ; Plants, Medicinal ; genetics ; Swertia ; genetics ; Transcriptome

This study was aimed to prepare the spraying agent of prescriptions of Miao nationality herb and investigate the effect of Miao nationality herbs spray for serum SOD, MDA, and expression of Fas and Caspase-3 mRNA in lung tissues of silica-treated rats. The healthy SD rats were divided into 5 groups. Silica dust suspension was used in the model establishment of 4 groups. After the model was successfully established, 3 groups were randomly selected and given glucocorticoids atomization inhalation, Miao nationality herbs spray, Miao nationality herbs spray combined with intragastric administration of herbal medicine, respectively. After 40-day treatment, water-solubletetrazolium salt (WST-1) was used in the detection of serum superoxide dismutase (SOD). Thiobarbituric acid (TBA) was used in the detection of malondialdehyde (MDA). The mRNA expression variance of the Fas and Caspase-3 were detected by RT-PCR. The results showed that compared with the silica dust suspension group, the SOD activity of serum in the Miao nationality herbs spray group was significantly increased (P< 0.05). MDA content and the mRNA of Fas and Caspase-3 were significantly lower in the Miao nationality herbs spray group (P< 0.05). It was concluded that Miao nationality herbs spray group was able to increase the SOD activity of serum, decrease MDA content, and obviously decrease the expression of Fas and Caspase-3 of lung tissues among silica dust suspension rats.

Objective To investigate the nucleotide-binding oligomerization domain-2(NOD-2)gene expression in deep caries and the effects of NOD-2 agonist muramyl dipeptide(MDP)on the differentiation of human dental pulp cells(hDPC). Methods NOD-2 gene level in deep caries and healthy pulp tissue was determined by real-time quantitative polymerase chain reaction(realtime-PCR). Realtime-PCR,Western blotting and immunofluorescence were performed to evaluate NOD-2 gene and protein expression. Dentin sialoprotein(DSP)protein level was assessed when hDPC were challenged by different concentrations of MDP for 24 hours, and sialophosphoprotein(DSPP), osteocalcin(OCN)mRNA and osteopontin(OPN)protein level were detected at different time points after incubation with 0.1 mg/L MDP. Results NOD-2 mRNA level was higher in pulp tissue of deep caries(0.2610±0.0824) than that in healthy controls(0.0024±0.0002),P<0.05.The expression of NOD-2 gene and protein increased in a time denpendent manner upon stimulation with MDP. Immunofluorescence confirmed that NOD-2 protein was located in cytoplasm. Moreover, 0.1 mg/L MDP augmented DSP protein level. DSPP and OCN mRNA were elevated with time and reached the peak at 12 h and down-regulated. OPN protein level also increased with time. Conclusions Dental pulp NOD-2 expression are up-regulated in pulp tissue of deep caries. MDP may be related to the differentiation of hDPC.