ObjectiveTo investigate differential metabolites associated with browning in the post-harvest processing of Pinelliae Rhizoma， providing data support for elucidating the key metabolites and metabolic pathways involved in browning， and developing safe and efficient sulfur-free processing techniques. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS） was used to detect the metabolites of Pinelliae Rhizoma at different browning stages（0， 8， 16 h） for widely targeted metabolomics. Subsequently， Multivariate statistical analysis of metabolites was conducted using principal component analysis（PCA）， hierarchical cluster analysis（HCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， and K-means cluster analysis. Differential metabolites at different browning stages were screened based on variable importance in the projection（VIP） value>1 and |log₂fold change（FC）|≥1， and metabolic pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsA total of 1 416 metabolites were identified across the three browning stages of Pinelliae Rhizoma， predominantly comprising amino acids and their derivatives（239）， lipids（219）， alkaloids（156）， phenolic acids（121）， terpenoids（113）， and flavonoids（111）. A two-by-two comparison of the three browning phases， yielded 622 differential metabolites that were significantly enriched in the phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolic pathway. Further analysis revealed that carbohydrates such as D-mannose and turanose， phenolic acids such as 1-O-caffeoyl-6-O-glucosyl-β-D-glucose， dicaffeoylshikimic acid， and flavonoids such as epigallocatechin gallate， vitexin-7-O-rutinoside， luteolin-7-O-（6″-malonyl）glucoside-5-O-arabinoside， catechin gallate， epicatechin gallate， isovitexin-7-O-glucoside-2″-O-rhamnoside， apigenin-7-O-rutinoside-4ʹ-O-sophoroside， 3，5，3ʹ，4ʹ，5ʹ-penta-hydroxyflavan-7-gallate may act as browning substrates and play important roles in the browning process. ConclusionCarbohydrates， phenolic acids， and flavonoids may serve as key substrates in the browning process of Pinelliae Rhizoma， involving pathways such as phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolism， which can provide a theoretical basis for further exploration of the browning mechanism.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.
Humans ; RNA, Untranslated/genetics* ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; RNA, Circular ; Central Nervous System Diseases/genetics*

Objective:To systematically review the severe risk in common chronic diseases and coronavirus disease 2019 (COVID-19) cases.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, medRxiv, SSRN and ChinaXiv were searched for clinical and epidemiological studies that reported chronic diseases in patients with COVID-19. Only studies of severe COVID-19 in comparison with non-severe controls were included. The prevalence rates of chronic diseases including chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, malignant tumor, cardiovascular diseases, cerebrovascular disease, chronic kidney disease, and chronic liver disease were estimated. Pooled odds ratio ( OR) with 95% confidence interval ( CI) between patients with severe COVID-19 and non-severe groups were calculated. R 3.6.3 software was used for meta-analysis. Results:The search yielded 2 455 articles. A total of 19 eligible comparative studies with 4 792 patients were included in a quantitative analysis. Meta-analysis showed that there was a proportion of 55.0% (95% CI 40.0%-80.0%) male among patients with COVID-19, and the overall pooled prevalence of any chronic diseases in COVID-19 cases was 30.4% (95% CI 24.0%-37.0%). The most prevalent comorbidity was hypertension (16.9%(95% CI 14.0%-20.0%)), followed by diabetes mellitus (8.3%(95% CI 8.0%-9.0%)). The proportion of male patients with severe COVID-19 was higher than that of male patients with non-severe COVID-19 (64.4% vs 52.8%, OR=1.49, 95% CI 1.08-2.05, Z=4.63, P<0.01). The prevalence rates of COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor in severe COVID-19 patients were higher than those of non-severe patients ( OR=5.77, 95% CI 3.80-8.74; OR=4.47, 95% CI 2.71-7.38; OR=3.55, 95% CI 2.86-4.40; OR=3.05, 95% CI=1.76-5.28; OR=2.82, 95% CI=1.96-3.97; OR=2.39, 95% CI=1.77-3.23; OR=2.15, 95% CI 1.27-3.66, respectively, Z=8.37, 6.01, 11.60, 4.20, 5.46, 5.71, 3.12, all P<0.01). There was no significant difference in the prevalence of chronic liver disease between severe and non-severe patients ( OR=1.35, 95% CI 0.84-2.17, P=0.11). Conclusion:COVID-19 patients with chronic diseases have higher risk of developing severe disease, and the ORs from high to low are COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor.

Objective To investigate the red blood cell distribution width (RDWC)and serum leptin (Leotin)levels in pa-tients with early onset coronary heart disease (CHD)and their correlation.Methods From January 2013 to April 2016,320 cases of hospitalized patients with chest pain,chest tightness in the cardiovascular department of the Gaoming District People's Hospital of Foshan City,Guangdong Province,were examined by coronary artery.Of which 240 cases were male under 55 years old,female under 65 years old patients with coronary heart disease (coronary heart disease group),another 80 cases of normal coronary angiography and treadmill negative males under 5 5 years old,female under 6 5 years old patients,as the con-trol group.Gensini score in patients with premature coronary heart disease was calculated according to the coronary artery imaging results,Comparison between the two groups of red blood cell distribution width and serum leptin levels were differ-ent,analysis of red blood cell distribution width and serum leptin levels and the correlation between the degree of coronary artery lesions.Results The red blood cell distribution width and the serum leptin level in patients with early onset coronary heart disease were (13.87 ± 0.31)% and (12.24 ± 2.21)μg/L,significantly higher than the control group (14.31 ± 0.22)% and (9.21±1.78)μg/L (t=11.742,11.116,P<0.001).And Gensini score was positively correlated with coro-nary artery (r=0.413,0.124,P=0.000,0.041).Correlation of red cell distribution width and serum leptin levels were posi-tively (r=0.107,P=0.008).The research object curve the predictive value of red cell distribution width in patients with premature coronary heart disease (ROC)analysis showed that the area of ROC curve of red cell distribution width (AUC) under 0.725(95%CI:0.679~0.764),red cell distribution width value 12.85%,the sensitivity was 68.1%,specificity was 65.4%.Conclusion In patients with premature coronary heart disease,the red blood cell distribution width and serum leptin levels were significantly increased,and was positively correlated with the degree of coronary artery disease,can be used as an independent predictor of premature coronary heart disease.

Objective To observe the effect of EGFR‐TKI combined with chemotherapy on the changes of serum insulin‐like growth factor1(IGF‐1)and anterior gradient‐2(AGR2)levels in the patients with advanced non‐small cell lung cancer(NSCLC) ,and to investigate whether IGF‐1 and AGR2 can serve as a potential indicator of the prognosis and efficacy of chemotherapy in NSCLC . Methods Sixty‐eight patients with advanced NSCLC were selected as the experimental group treated by EGFR‐TKI combined chemotherapy and 30 healthy people served as the healthy control group .(treatment group) .The levels of serum IGF‐1 and AGR2 before chemotherapy and at 3 weeks after chemotherapy were detected by ELISA .The influence of serum IGF‐1 and AGR2 levels on the prognosis was analyzed by using Kanplan‐Meier method .Results (1)The disease control rate(DCR)in the EGFR‐TKI com‐bined chemotherapy was 52 .9% ;(2)the level of serum IGF‐1 before treatment in the experimental group was (329 .35 ± 88 .13)μg/L ,which was significantly higher than (146 .36 ± 41 .27)μg/L in the healthy control group(P<0 .01);the level of serum AGR2 in experimental group was(16 .72 ± 6 .23)ng/mL ,which was significantly higher than (4 .38 ± 2 .17)ng/mL in the healthy control group(P<0 .01);serum levels of IGF‐1 and AGR2 after treatment were(211 .53 ± 52 .31)μg/L and (9 .72 ± 3 .56)ng/mL respec‐tively ,which were significantly lower than those before treatment (P<0 .01);serum IGF‐1 and AGR2 in NSCLC patients were pos‐itively correlated(r=0 .489 ,P<0 .01);(3)serum levels of IGF‐1 and AGR2 after chemotherapy were(128 .62 ± 48 .24)μg/L and (7 .22 ± 4 .27)ng/mL respectively ,which were obviously lower than(334 .23 ± 82 .11)μg/L and(18 .43 ± 6 .17)ng/mL before chem‐otherapy(all P<0 .01) .The Kanplan‐Meier analysis revealed that serum IGF‐1 and AGR2 levels in advanced NSCLC had an obvi‐ous influence on the prognosis .Conclusion Serum IGF‐l and AGR2 levels may have a potential clinical value to assess the therapeu‐tic efficacy of EGFR‐TKI combined chemotherapy and prognosis in advanced NSCLC .

Adenocarcinoma ; diagnosis ; surgery ; Helicobacter Infections ; diagnosis ; Humans ; Lymphoma, B-Cell, Marginal Zone ; diagnosis ; surgery ; Male ; Middle Aged ; Stomach Neoplasms ; diagnosis ; surgery

OBJECTIVETo investigate the effect of intensive rosuvastatin therapy on adhesion molecules in patients with peripheral atherosclerosis and explore the possible upstream mechanism.

METHODSTwenty asymptomatic patients with peripheral atherosclerosis were enrolled and given 5-20 mg/day rosuvastatin for 3 months. Before and after the treatment, the lipid profile and plasma vascular cell adhesion molecule-1 (VCAM-1) levels were examined. The expression of intercellular adhesion molecule-1 (ICAM-1) in the mononuclear cells was measured using flow cytometry, and the mRNA and protein expressions of peroxisome proliferator-activated receptor γ (PPARγ) were detected using RT-PCR and Western blotting, respectively.

RESULTSCompared with the baseline levels, ICAM-1 expression decreased and PPARγ protein expression increased in the lymphocytes. Rosuvastatin therapy did not produce obvious effects on plasma VCAM-1 level or ICAM-1 expression in the monocytes in these patients.

CONCLUSIONRosuvastatin produces anti-inflammatory effects by decreasing the expression of ICAM-1 in mononuclear cells, and its upstream mechanism may involve the PPARγ pathway.

Atherosclerosis ; drug therapy ; metabolism ; Cell Adhesion Molecules ; metabolism ; Female ; Fluorobenzenes ; administration & dosage ; therapeutic use ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Middle Aged ; Monocytes ; drug effects ; metabolism ; PPAR gamma ; metabolism ; Pyrimidines ; administration & dosage ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; administration & dosage ; therapeutic use ; Vascular Cell Adhesion Molecule-1 ; metabolism

We reported a rare case of protoplasmic astrocytoma presenting small muscle atrophy of the right hand as an initial sign.A 39-year-old male was admitted to hospital complaining of chronic muscle atrophy and subtle headache.Electromyography(EMG) showed brief small denervation and no signs of sensory-motor conduction impairment.CT and MRI revealed multiply expansive intracranial lesion in left hemisphere,which was highly suspected of cerebral echinococccus or Balo disease.The patient underwent surgical excision and pathological report was protoplasmic astrocytoma,with glial fibrillary acidic protein(GFAP,+++) of immunohistochemical method.We reviewed clinical features,radiological manifestations and pathology of protoplasmic astrocytoma with medical literature documents.

Objective To understand the histologic changes of prostatic carcinoma's bone metastases and other associated observations,and to provide histopathological basis for clinical therapy. Methods Seven patients with prostatic carcinoma bone metastases,whose needle biopsy of prostate and bone metastases was positive,were treated by hormone castrative therapy.The changes of prostatic primary carcinoma,bone metastases and correlated examinations were observed,and the results were compared with those before treatment. Results The prostatic tumors of 7 patients disappeared in 2 months after treatment.The prostate specific antigen (PSA) level of 5 patients returned to normal within 2 months.Two patients had orthopedics surgery because of spinal epidural compression symptom,and their pathologic examination of bone metastases showed that the transparent cells disappeared,the number of tumor bone trabecula reduced and immunohistochemical stains of PSA was negative.Another 2 patients had bone excision because of the development of bone metastases.Transparent acinose cells,mixed with many tumor-like bone tissues,could be found in the focus,with immunohistochemical stains being positive compatible with the changes of focal bone,PSA and imageology examination showed corresponding results. Conclusions Castration therapy can make carcinoma cells of the prostate and bone metastases,partially or completely,disappear.However,part of bone metastases changes may not be consistent with those of primary carcinoma.PSA and imageology examination may show the correlated changes of bone metastases,and provide exact basis for the clinical treatment.