[Objective]This study was aimed to research the synergistic antitumor proliferation effects and their best proportion of ursolic acid(UA) and tetrandrine(Tet), a pair of compounds isolated from Chinese herbs which showed complement inhibition on the multiple signal pathways. [Methods] The reporter assays on tumor-related signal pathways for MAPK/ERK, MAPK/JNK, NF-κB, Wnt, Notch, Cell Cycle, Myc/Max and Hypoxia were used to study the effect of five different Chinese herbal compounds on tumor proliferation,it was concluded cepharanthine(Cep), Tet, 18α-glycyrrhetinic acid(18α-Gly), UA and luteolin(Lut). MTT assay and crystal violet staining were used to study the antiproliferative effect of 15 different compounds for the tumor cells of MDA-MB-231,SW480,MG63,PC3,DU145,HCT116,143B and MDA-MB-468, which is consisted with Cep, Tet, 18α-Gly, UA and Lut for the 15 different compounds. Coefficient of drug interaction(CDI) method was used to detect the synergistic effect of the two compounds. Combination of index(CI) and isobologram method was used to screen the best ratio of compounds in their antiproliferative effects. [Results] The signal pathway reporter assay showed that UA and Tet could complementarily inhibit tumor-related signaling pathways. And the results also showed that UA and Tet could induce synergetic anti-tumor cell proliferation in vitro. Furthermore, the optimal ratio of UA and Tet was 9:1 by using isobologram and CI method. [Conclusion] UA and Tet can be inhibited and complemented by 8 tumor-related signaling pathways, and we used MTT assay and crystal violet staining or other methods to confirm the synergistic antitumor proliferation effects, furthermore, the optimal proportion for UA and Tet were screened, and it provided a new insight to develop new anticancer formula in research.

Objective To develop a method of detecting dry blood spot (DBS) samples collected in the filter paper by using Surface Enhanced Raman Spectroscopy (SERSp,also known as Raman molecular fingerprint spectrum) technology.The possibility and reliability of applying the technology to the newborn screening of congenital hypothyroidism (CH) was investigated.Methods The case-control study was used.The results of CH-hTSH screening test based on the DBS samples collected in the filter paper,and the clinical diagnosis were all provided by neonatal screening center of Shanghai Children's Hospital.The results of SERSp analysis were provided by Dalian University of Technology.Six positive and six negative samples,which were confirmed respectively by CH-hTSH screening using time resolved fluoroimmunoassay (TRFIA) were chosen.With the spectrum lines of 725 cm-1 as internal standard,the SERSp from the aqueous solution of these samples were analyzed.The specific spectrum line analysis,the principal component analysis (PCA) and the scatter diagram of PCA were used to compare the results of TSH test.Results With the spectrum lines of 725 cm-1 as internal standard,the CH specific spectrum lines of 1373 cm-1 and 1400 cm-1 were discovered.They showed the most significant difference of the peak height between the positive and negative samples of CH,while TSH specific spectrum lines of 785 cm-1,827 cm-1 and 853 cm-1 failed to distinguish positive from negative samples with distinct peak height.The consistency between the results of CH-Raman Screening and CH-hTSH Screening was 91.7％ (11/12),which was proven by PCA,the scatter diagram of PCA and the specific spectrum line analysis.The sensitivity of CH-Raman Screening was 100％ and the specificity was 83.3％.Conclusion There is a new CH-Raman Screening method using the SERSp analysis,which was proven to be a promising technology in the newborn screening of congenital hypothyroidism with the DBS in the filter paper.

Objective To investigate the expressions of ezrin,E-cadherin,paxillin and integrin β1 in skin squamous cell carcinoma (SCC) and their significance.Methods The expressions of ezrin,E-cadherin,paxillin and.integrin β1 were immunohistochemically detected in tissue specimens from 30 patients with SCC and 10 normal human controls.Results The expression rates of ezrin and E-cadherin in normal human keratinocytes were significantly higher than those in SCC cells [ 100.00％ (10/10)vs.56.67％(17/30),x2 =6.42,P ＜ 0.05; 100.00％ (10/10) vs 13.33％ (4/30),x2=24.76,P ＜ 0.05],while the expression rates of paxillin and integrin β1 in normal human keratinocytes were significantly lower than those in SCC cells [0.00vs.70.00％ (21/30),x2 =14.74,P ＜ 0.01; 10.00％ (1/10) vs.66.67％ (20/30),x2 =9.66,P ＜ 0.05].In SCC cells,there was a significant positive correlation between the expression of ezrin and E-cadherin (r =0.52,P ＜0.01 ),but a negative correlation between the expression of paxillin and E-cadherin and between that of integrin β1 and E-cadherin (r =- 0.56,- 0.52 respectively,both P ＜ 0.01); no significant correlation was observed between the expression of ezrin and paxillin or integrin β1,or between the that of paxillin and integrin β1 (r =0.5,0.24 and 0 respectively,all P ＞ 0.05).Conclusions The low expression of E-cadherin and high expression of paxillin and integrin β1 may synergistically promote the invasion and metastasis of tumor cells,while integrin β1 and E-cadherin may play an antagonistic role in the metastasis of SCC.

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Objective:To analyze the mortality of accidental falls among the elderly in China from 2004 to 2019 and predict the standardized mortality from 2020 to 2024, so as to provide scientific evidence for formulating strategies to prevent accidental falls among the elderly.Methods:The death data of accidental falls of the elderly in China from 2004 to 2019 were collected from the China Death Cause Monitoring Data Set, and the total number of deaths, mortality rate and standardized mortality rate in the elderly from 2004 to 2019 and those data among them of different genders, residences and age groups were calculated. Joinpoint 4.8.0.1 statistical software was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of standardized mortality. The Autoregressive Integrated Moving Average Model (ARIMA) was used to predict the standardized mortality rate of accidental falls among the elderly in China from 2020 to 2024. Results:The number of deaths related to accidental falls among the elderly in China was increased from 2 908 in 2004 to 23 709 in 2019. The mortality rate was increased from 51.89/100 000 in 2004 to 67.74/100 000 in 2019. The standardized mortality rate of accidental falls showed an overall upward trend from 2004 to 2019 (AAPC=1.65, P>0.05), including an upward trend from 2004 to 2010 (APC=1.66, P>0.05), a downward trend from 2010 to 2013 (APC=-9.67, P>0.05), and another upward trend from 2013 to 2019 (APC=7.83, P<0.01). The number of death and mortality rate related to accidental falls in Chinese elderly males and females both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed upward trends from 2004 to 2019 (AAPC males=2.19, AAPC females=0.29, all P>0.05). The standardized mortality rate in males was generally higher than that in females, with that of males showing an upward trend from 2013 to 2019 (APC=7.36, P<0.05) and that of female showing an upward trend from 2014 to2019 (APC=6.92, P>0.05). The number of deaths and mortality rate among the elderly living in rural and urban areas both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed an upward trend from 2004 to 2019 (AAPC rural = 1.71, AAPC urban =1.00, all P>0.05). The standardized mortality rate among the elderly living in rural areas was generally higher than that in urban areas. The rural and urban elderly both showed upward trends from 2013 to 2019 (APC rural = 8.24, APC urban =6.11, all P<0.05). The number of death and mortality rate of different age groups all showed upward trends from 2004 to 2019. The standardized mortality rates of the elderly aged 65-74 years and ≥85 years also showed upward trends from 2004 to 2019 (AAPC 65-74 years=0.38, AAPC ≥ 85 years=4.09, all P>0.05). The standardized mortality rate of the elderly aged 75-84 years showed a downward trend from 2004 to 2019 (AAPC=-0.10, P>0.05), and that of the elderly aged 65-74 years showed an upward trend from 2010 to 2019 (APC=5.35, P<0.05). The standardized mortality rate of the elderly aged 75-84 years and ≥85 years showed upward trends from 2013 to 2019 (APC 75-84 years=6.49, APC ≥ 85 years=10.47, all P<0.05). The ARIMA prediction results showed that the overall standardized mortality rates of accidental falls in the elderly in China from 2020 to 2024 were 69.11/100 000, 72.33/100 000, 74.41/100 000, 76.34/100 000, and 76.48/100 000, respectively, showing a slow upward trend. Conclusions:The accidental fall-related mortality among the elderly in China showed an overall upward trend from 2004 to 2019, and the standardized mortality rate from 2020 to 2024 also shows an upward trend. The elderly who are male in gender, live in rural areas, or at age of ≥85 years are the key population for prevention and control of accidental fall. Active and effective measures should be taken to reduce accidental falls in the elderly so as to contribute to active and healthy aging.

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.

Dioscoreae Rhizoma formula granules are made from decoction pieces by decocting， extracting， separating， concentrating， drying and granulating， which have the advantages of simple dispensing， convenient use and easy to take without decoction. However， because Dioscoreae Rhizoma is rich in starch and mucus components， its extract powder and formula granules are poorly soluble and difficult to dissolve or disperse completely within 5 min， and the insoluble material is difficult to dissolve completely even after 24 h in water， which affects the quality evaluation of the formula granules and medication psychology of patients. Therefore， by studying the dissolution process and mechanism of Dioscoreae Rhizoma extract and its formula granules， it was found that the special chemical composition of Dioscoreae Rhizoma， the denaturation of starch and its compounding with protein and other substances during the high temperature extraction process， and the contraction of coating membrane during the spray drying process were combined to form the special microstructure of coating membrane covering starch granules， and it is the root cause of poor solubility of Dioscoreae Rhizoma formula granules. Based on the research on the structure， property and function of the powder， this paper proposed a technical strategy to improve the solubility of Dioscoreae Rhizoma formula granules by powder modification process， and experimentally demonstrated that the modified Dioscoreae Rhizoma formula granules could completely dissolve within 2 min， which solved the technical problem and could provide reference for the improvement of solubility of other similar varieties， and promote the high-quality development of traditional Chinese medicine formula granule industry.