Pulmonary fibrosis is a chronic， progressive and irreversible interstitial lung disease. At present， there is no specific drug for the treatment of pulmonary fibrosis， and many TCM monomers have potential therapeutic value for pulmonary fibrosis， among which flavonoids are the main representative. For example， total flavones of Astragalus memeranaceus and scutellarin can reduce inflammatory cell infiltration， lung injury and extracellular matrix （ECM） deposition by interfering with transforming growth factor-β1/drosophila MAD protein signaling pathway. Total flavonoids of Oxytropis falcata Bunge and salidroside can inhibit lung inflammation by mediating JAK/signal transduction and transcriptional activator signaling pathway， and prevent the epithelial interstitial transition （EMT） process. Quercetin and Ginkgo biloba leaf extract can reduce the apoptosis of macrophages by inhibiting the nuclear factor-κB signaling pathway and play an anti-pulmonary fibrosis role. Urushetin and proanthocyanidins can promote the morphological recovery of myofibroblasts and reduce ECM deposition through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target protein of rapamycin signaling pathway. Naringin and luteolin can inhibit scorch death of macrophage and inflammation response， and improve lung function and lung tissue injury through NOD-like receptor heat protein domain related protein 3 signaling pathway. The ethanol extract of Phyllanthus emblica and calycosin can improve the inflammatory injury and fibrosis of lung tissue by activating the signaling pathway of nuclear transcription factor erythro2-related factor 2/antioxidant response element. Isogliquiritin can inhibit the phenotypic transformation of epithelial cells and reverse EMT progression by inhibiting extracellular signal-regulating kinase signaling pathway. In the future， scholars should consider developing appropriate drug carriers to improve their bioavailability and further study drug targets and pathways， to provide evidence for the development of traditional Chinese medicine monomers of flavonoids into clinical practice.

【Objective】 To investigate the effects and mechanisms of different doses of fingolimod (FTY720) on non-antibody-mediated transfusion-related acute lung injury (TRALI). 【Methods】 A TRALI mouse model was constructed using lipopolysaccharide (LPS) pre-stimulation and platelets (Plt) of different storage days for second strike. The success of the modeling was determined by protein concentration in lung tissue homogenates, myeloperoxidase (MPo) activity, lung wet/dry weight ratio (W/D ratio), lung tissue damage score and pathological sections. Ceramide and sphingosine-1-phosphate (S1P) contents in platelets of different storage days were detected. FTY720 was administered 1 h after LPS injection to investigate the role of FTY720 in TRALI. The expression levels of vascular endothelial cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) were analyzed by WB. 【Results】 Mice infused with stored 5-day Plt (d5Plt group) exhibited typical signs of TRALI, and the differences in lung tissue homogenate protein concentration (6 546.38±409.50) μg/mL, MPO activity (49.38±4.43) U/L, W/D ratio 4.79±0.21, and lung tissue damage score 7.24±0.38 from the rest of the groups were statistically significant (P<0.05). With the increase of platelet storage time, the ceramide content gradually increased and S1P content gradually decreased, and the ratio of the two was imbalanced. d5Plt showed statistically significant differences (P<0.01) in ceramide content (58.37±5.69) μmol/L and S1P content (149.81±4.86) nmol/L from the rest of the groups. After preventive administration of FTY720, 1 mg/kg FTY720 had no significant effect on TRALI mice, whose lung tissue homogenate protein concentration (6 170.26±545.50) μg/mL, MPO activity (45.97±4.79) U/L, W/D ratio 4.88±0.25, and lung tissue damage score 7.92±0.65 were significantly higher than those of the normal and LPS control groups (P<0.01). The low-dose (0.5, 0.2, and 0.1 mg/kg) FTY720 group alleviated lung injury, and its protein concentration, MPO activity, W/D ratio, and lung tissue injury score were significantly lower than those of the d5Plt group (P<0.05). Pathological sections also showed similar results. In terms of endothelial intercellular junction protein expression, the VE-cadherin expression levels in the 1 mg/kg FTY720 group were significantly lower than those in the normal and LPS control groups (P<0.05), and the VE-cadherin and ZO-1 expression levels in the low-dose (0.5, 0.2, and 0.1 mg/kg) FTY720 group were significantly higher than those in the d5Plt group (P<0.05), which tended to be normalized. 【Conclusion】 In this study, a TRALI mouse model was successfully established by one strike of LPS and two strikes of d5Plt. Low doses of FTY720 (0.5, 0.2, 0.1 mg/kg) were protective against TRALI, while high doses of FTY720 (1 mg/kg) may aggravate the symptoms of TRALI. This protective effect may be somewhat dependent on the expression of VE-cadherin and ZO-1.

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.
Humans ; Irinotecan ; Colorectal Neoplasms/genetics* ; Resveratrol ; Molecular Docking Simulation ; ErbB Receptors/genetics*

Wild castor grows in the high-altitude tropical desert of the African Plateau,a region known for high ultraviolet radiation,strong light,and extremely dry condition.To investigate the potential genetic basis of adaptation to both highland and tropical deserts,we generated a chromosome-level genome sequence assembly of the wild castor accession WT05,with a genome size of 316 Mb,a scaffold N50 of 31.93 Mb,and a contig N50 of 8.96 Mb,respectively.Compared with cultivated castor and other Euphorbiaceae species,the wild castor exhibits positive selection and gene family expansion for genes involved in DNA repair,photosynthesis,and abiotic stress responses.Genetic variations associated with positive selection were identified in several key genes,such as LIG1,DDB2,and RECGI,involved in nucleotide excision repair.Moreover,a study of genomic diversity among wild and cultivated accessions revealed genomic regions containing selection signatures associated with the adaptation to extreme environments.The identification of the genes and alleles with selection signatures provides insights into the genetic mechanisms under-lying the adaptation of wild castor to the high-altitude tropical desert and would facilitate direct improvement of modern castor varieties.

Accidents, Traffic ; Forensic Medicine ; Hoarseness ; Humans

In this study, physical fingerprint and multivariate statistical analysis was applied to characterize the quality consistency of different sources of carboxymethylcellulose sodium, and the visualization of R language was used to explore the intrinsic correlation on its performances, and we drew contour maps between independent variables and flowability of powder to find the design space. Through the physical fingerprint and multivariate statistical analysis, it was found that there were differences in the powder properties of carboxymethylcellulose sodium from different sources, and its moisture content, bulk density and tapped density have a great influence on the fluidity. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by R intelligent visualization analysis, which was statistically significant (P < 0.01). When the angle of repose is 30° - 40°, the appropriate design space was found as 5.092 2% < moisture content < 7.006 7%, 0.560 2 g·cm^-3 < bulk density < 0.579 9 g·cm^-3, and 0.646 3 g·cm^-3 < tapped density < 0.816 5 g·cm^-3. The results show that it is scientific and feasible to evaluate the quality consistency of pharmaceutical excipients by using the physical fingerprint, multivariate statistical analysis and visualization methods, which provides new ideas for the production and quality evaluation of excipients and the development of generic prescriptions.

Objective: To investigate the value of pulmonary ventilation/perfusion (V/Q) SPECT imaging in fibrosing mediastinitis (FM). Methods: From January 2015 to July 2018, 14 FM patients (6 males, 8 females, average age 74 years) who underwent V/Q SPECT imaging in China-Japan Friendship Hospital were retrospectively studied. The data of V/Q SPECT imaging were analyzed and the defect extent was classified as mild (<20%), moderate (20%-50%) and severe (>50%) according to the percentage of pulmonary perfusion and ventilation defect in total lung volume (%). χ² test was used to analyze the incidence rates of the impaired blood perfusion of each lung lobe. Results: According to the results of Q SPECT imaging, all 14 patients had impaired blood perfusion in the superior lobe of left lung, and the number of patients with/without impaired blood perfusion in the inferior lobe of left lung, superior lobe of right lung, middle lobe of right lung, inferior lobe of right lung were 11/3, 14/0, 13/1, 12/2, respectively. The incidence rates of impaired blood perfusion in different lobes were not significantly different (χ²=6.198, P=0.185). The range of lung perfusion defect was mild in 1, moderate in 7 and severe in 6 patients. The incidence rates of impaired blood ventilation in different lobes were not significantly different (χ²=1.587, P=0.811). The range of lung ventilation defeat was mild in 11, moderate in 2 and severe in 1 patients. The defect extent of lung segments and subsegments in Q SPECT imaging and V SPECT imaging were 119 and 41, respectively (χ²=28.42, P<0.05). There was more defect in Q SPECT imaging, but both methods showed segmental or subsegmental distribution. Conclusions The defect of V/Q SPECT imaging in FM patients is segmental in distribution, and more is observed in Q SPECT imaging. Pulmonary V/Q SPECT imaging can evaluate the defect range and extent of pulmonary perfusion and ventilation in FM patients.

【Background】 The aim of this prospective randomized study was to evaluate the feasibility of subtotal thyroidectomy leaving a unilateral remnant based on the upper pole. 【Methods】 Patients who underwent the subtotal thyroidectomy and isthmusectomy leaving either a unilateral remnant based on the upper pole（GroupⅠ ，59 patients）or with the bilateral dorsal thyroid tissue remained（Group Ⅱ，54 patients）were prospectively compared in operation time， blood loss，recurrence，and postoperative complications.【Results】The operation time remained similar between the two groups，but the blood loss，the reoperation time，recurrent laryngeal nerve injury，and recurrence in GroupⅠwere much less than those in Group Ⅱ. In addition ，no postoperative hemorrhage occurred in GroupⅠ. Three patients （5.56%） underwent postoperative hemorrhage in Group Ⅱ. Two patients（3.39%）in GroupⅠand 4 patients（7.40%）in Group Ⅱ experienced transient hypocalcemia.【Conclusion】In terms of blood loss，reoperation time，postoperative complication， and recurrence ，subtotal thyroidectomy with recurrent laryngeal nerves identification and the unilateral superior pole remnant of the gland provides a better outcome than subtotal thyroidectomy with bilateral dorsal thyroid tissue remnant.

Objective To research the correlation between the visual acuity ratio and pattern reversal visual evoked potential （PRVEP） P100 waveform amplitude ratio of both eyes. Methods Forty-seven volunteers were selected, and the visual chart visual acuity of both eyes was measured. The visual acuity ratio of the eye with poor vision to the eye with better vision was calculated by five grade notation method. The amplitudes of P100 waveforms of both eyes were recorded respectively by using black-and-white checkerboard PRVEP and chosing 1°, 15' stimulating visual angle, and the ratio of amplitudes between the two eyes was also calculated. SPSS 20.0 software was used to analyze the correlation between the visual acuity ratio and the ratio of P100 waveform amplitudes between the two eyes. Return test and linear regression analysis with the binocular ratio of P100 waveform amplitudes as the independent variable （x） and the binocular visual acuity ratio as the dependent variable （y） were made. Results There was a positive correlation between the binocular visual acuity ratio and the ratio of P100 waveform amplitudes under 15' stimulating visual angle （Pearson correlation coefficient was 0.62, P=0.000）. The fitting linear regression equation was y=0.090 x+0.846 （F=20.954, P=0.000）. There was no significant correlation between the binocular ratio of visual acuity and the binocular ratio of P100 waveform amplitudes under 1° stimulating visual angle （P>0.05）. Results of return test showed that there was no statistical significance in the difference between visual acuity estimated by equation and actual detected visual acuity. Conclusion In forensic appraisal of monocular injury, fitting linear regression equation of binocular visual acuity ratio and the binocular ratio of P100 waveform amplitudes under 15' stimulating visual angle, is helpful for visual acuity level estimation of the injured eye to some extent.
Evoked Potentials, Visual ; Eye/physiopathology* ; Humans ; Regression Analysis ; Vision, Ocular ; Visual Acuity

Gradation of Disability in Human Body Injuries （hereinafter referred to as Gradation） has been released and used since January 2017, and has become the most widely used standard in forensic science practice. This paper calculates and rates the visual system evaluation provisions of the current domestic disability evaluation criteria represented by the Gradation which used the methods of Guides to the Evaluation of Permanent Impairment （hereinafter referred to as GEPI） issued by American Medical Association （AMA）. Through comparing, a good correlation between the provisions in Gradation and whole person impairment rating index in GEPI was shown. On the basis of this, suggestions are put forward to amend some provisions of Gradation, in order to provide reference for the revision and further improvement of domestic standards and provisions.
American Medical Association ; China ; Disability Evaluation ; Disabled Persons ; Forensic Medicine/standards* ; Forensic Sciences ; Guidelines as Topic ; Humans ; United States