Research progress in roles of fibroblast activation in tissue fibrosis,autoimmune diseases and tumor disease / 中国药理学与毒理学杂志

Fibroblasts are stromal cells widely distributed in tissues and organs throughout the body.Fibroblasts are involved in the synthesis and remodelling of the extracellular matrix.Fibroblasts participate in physiopathological processes such as tissue damage repair,inflammatory responses and immune regulation.Large numbers of activated fibroblasts have been found in fibrosis,autoimmune diseases and tumor lesions.Activated fibroblasts participate in tissue fibrosis and influence the tumor microenvi-ronment mainly by secreting collagen and fibronectin.They also secrete a variety of inflammatory and growth factors that play an immunomodulatory role in autoimmunity and tumors.In recent years,it has been found that modulating fibroblast activation can effectively delay the development of these diseases,and that targeting fibroblast activation biomarkers can assess the development and treatment of these diseases.Therefore,the use of fibroblast-targeted drugs and therapeutic tools is expected to achieve new breakthroughs in the clinical management of fibrosis,autoimmune diseases and tumors.

Natural products in the prevention and treatment of melanoma / 药学学报

The incidence of malignant melanoma, a highly fatal skin tumor, is on the rise worldwide. Melanomas are highly aggressive and have strong metastatic capability that leads to lethality. Recurrence occurs in patients with distant metastases, even with the latest treatments, and median survival is only a few months. At present, the prevention and treatment of melanoma includes surgical resection, chemotherapy, immunotherapy and targeted therapy. However, these strategies can lead to drug resistance and adverse effects. In recent years, an increasing number of studies have found that natural products have effective anti-melanoma activities, including inhibition of tumor growth, induction of cell apoptosis, inhibition of angiogenesis and metastasis and toxicity to tumor stem cells. In addition, several studies have reported that the combination of natural products and traditional anti-melanoma drugs can enhance the therapeutic efficacy. In this review we summarize the prevention and treatment of melanoma with natural products.

Expression of thymidylate synthase in salivary adenoid myoepithelial cells and its clinical significance / 南方医科大学学报

OBJECTIVE@#To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance.@*METHODS@#Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100.@*RESULTS@#The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (>0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%.@*CONCLUSIONS@#TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.

Application of early goal-directed sedation with bispectral index in sedation management of severe patients in ICU / 中国医师杂志

Objective The bispectral index (BIS) was introduced into the sedation strategy of critical patients in intensive care unit (ICU) and replaced the Richmond agitation sedation scale (RASS).The ventilation time,ICU length of stay,and 90-day mortality were compared between the two groups of patients who performed early goal-directed sedation (EGDS) or standard traditional directed sedation (STDS) strategies.Methods A prospective controlled study of severe patients with mechanical ventilation ≥48 h in ICU (20 cases from April 2016 to May 2017,46 cases from June 2017 to April 2018) were randomly divided into EGDS or STDS group.There were no significant differences in age,gender,and acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ) score between the two groups in the two periods.The correlation between RASS and BIS was analyzed in the first period.The BIS of the patients in a RASS range of (-2-1) was 73.65 ± 7.87 in the EGDS group,and that of RASS range of (-3--1) was 64.14 ± 7.25 in the STDS group.The above BIS was applied to the two sedation strategies in the second period respectively.The ventilation time,ICU length of stay,and 90-day mortality were recorded.Results There was no significant difference in the ventilation time between the two groups [(164.12 ± 137.96) h and (155.33 ±64.86)h,P =0.08].ICU length of stay of the EGDS group was longer than that of the STDS group.The 90-day mortality of the EGDS group was higher than that of the STDS group.Conclusions Correlations between RASS and BIS were found in this study,and BIS can be used for sedation assessment in ICU patients.Large sample study is still needed to compare EGDS and STDS with BIS.

Chemical Constituents in Endophytic Fungus Nigrospora oryzae from Cordyceps / 中国实验方剂学杂志

Objective: To study the chemical constituents in theendophytic fungus Nigrospora oryzae from Cordyceps. Method: It was cultured with brownrice,and isolated and purified by chromatographic procedures, and the compounds were identified by NMR,ESI-MS and other spectral methods. Result: Totally 15 compounds were identified as mellein (1),linoleic acid (2),2-(2-hydroxyethyl)phenol (3),(3R)-mellein methyl ether (4),(3R,4S)-4-hydroxymellein (5),2-hydroxybenzaldehyde (6),3-phenylpropane-1,2-diol (7),1-phenyl-1,2-ethanediol (8),cyclo-(R-Prommmm-S-Ile) (9),cyclo-(D-Pro-L-Leu) (10),2-hydroxybenzaldehyde (11),4-hydroxy-8-O-methylmellein (12),cyclo-(S-Pro-S-Phe) (13),cyclo-(D-Pro-L-Ile) (14),cyclo-(D-Pro-L-Leu) (15). Conclusion: Compounds 1-15 were isolated from this fungus for the first time.

Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a systematic review and meta-analysis of six randomized controlled trials / Efeitos da pressão positiva contínua nas vias aéreas na pressão arterial em pacientes com hipertensão resistente e apneia obstrutiva do sono: revisão sistemática e meta-análise de seis ensaios clínicos controlados aleatórios

ABSTRACT Objective: To evaluate systematically the effects of continuous positive airway pressure (CPAP) on blood pressure in patients with resistant hypertension and obstructive sleep apnea (OSA). Methods: The Cochrane Library, PubMed, ScienceDirect, and the Web of Science were searched for studies investigating the effects of CPAP on blood pressure in patients with resistant hypertension and OSA. The selected studies underwent quality assessment and meta-analysis, as well as being tested for heterogeneity. Results: Six randomized controlled trials were included in the meta-analysis. The pooled estimates of the changes in mean systolic blood pressure and mean diastolic blood pressure (as assessed by 24-h ambulatory blood pressure monitoring) were −5.40 mmHg (95% CI: −9.17 to −1.64; p = 0.001; I2 = 74%) and −3.86 mmHg (95% CI: −6.41 to −1.30; p = 0.00001; I2 = 79%), respectively. Conclusions: CPAP therapy can significantly reduce blood pressure in patients with resistant hypertension and OSA.

RESUMO Objetivo: Avaliar sistematicamente os efeitos da continuous positive airway pressure (CPAP, pressão positiva contínua nas vias aéreas) na pressão arterial em pacientes com hipertensão resistente e apneia obstrutiva do sono (AOS). Métodos: Estudos que investigassem os efeitos da CPAP na pressão arterial em pacientes com hipertensão resistente e AOS foram buscados nos seguintes bancos de dados eletrônicos: Cochrane Library; PubMed; ScienceDirect e Web of Science. Os estudos selecionados foram submetidos a avaliação de qualidade, meta-análise e teste de heterogeneidade. Resultados: Foram incluídos na meta-análise seis ensaios clínicos controlados aleatórios. As estimativas combinadas das alterações das médias de pressão arterial sistólica e pressão arterial diastólica (medidas por meio de monitoração ambulatorial da pressão arterial durante 24 h) foram de −5,40 mmHg (IC95%: −9,17 a −1,64; p = 0,001; I2 = 74%) e −3,86 mmHg (IC95%: −6,41 a −1,30; p = 0,00001; I2 = 79%), respectivamente. Conclusões: O tratamento com CPAP é capaz de reduzir significativamente a pressão arterial em pacientes com hipertensão resistente e AOS.

Comparison of expandable intramedullary nail versus locked compression plate for treatment of humeral shaft fractures / 中华创伤骨科杂志

Objective To compare the effectiveness of expandable intramedullary nail(EIMN) versus locked compression plate (LCP) in the treatment of humeral shaft fractures of AO types A and B.Methods The clinical data were retrospectively analyzed and compared of the 44 humeral shaft fractures which had been treated between May 2012 and February 2016.There were 26 men and 18 women,from 23 to 66 years of age (average,41.5 years).By AO classification,22 cases were type 12-A and 22 type 12-B.EINM was used in 22 patients with an average age of 41.3 ± 1 1.7 years and LCP in 22 ones with an average age of 41.6 ± 10.3 years.The 2 groups were compared in terms of intraoperative blood loss,operative time,hospital stay,union time,union rate,Constant and Mayo scores at the final follow-ups,and complications as well.Results The 2 groups were compatible without significant differences in the preoperative demographic data (P ＞ 0.05).All the 44 patients were followed up for 10 to 18 months (average,12 months).The intraoperative blood loss (76.4 ± 18.66 mL),operative time (69.1 ± 13.2 min),incision length (5.8 ± 1.5 cm) and union time (13.2 ± 8.4 w) in the EIMN group were significantly better than those in the LCP group (138.6 ± 39.4 mL,96.4 ± 14.2 min,8.5 ± 1.4 cm and 18.4 ± 6.6 w,respectively) (P ＜ 0.05).There was also a significant difference between the 2 groups in the total complication rate[18.2％ (4/22) versus 50.0％ (11/22)] (P ＜0.05).No deep infection or should pain was observed in either group.Conclusions Inthe treatment of humeral shaft fractures of AO types 42-A and 42-B,compared with LCP,EIMN may have advantages of less intraoperative blood loss,operative time,union time and complications.The 2 methods are similar in hospital stay and final functional recovery of the should joint.

Prediction and identification of B-cell linear epitopes of hepatitis B e antigen / 南方医科大学学报

<p><b>OBJECTIVE</b>To predict and identify B-cell linear epitopes of hepatitis B e antigen (HBeAg).</p><p><b>METHODS</b>The B-cell linear epitopes of HBeAg were predicted using the software provided by NCBI Database and Immune Epitope Database (IEDB) and synthesized by a solid-phase method followed by conjugation with keyhole limpet hemocyanin (KLH). The KLH conjugates were used for immunization of New Zealand white rabbits, and the immune response of the rabbits was monitored by direct ELISA using a bovine serum albumin conjugate of the predicted epitopes. RESULTS Four new B-cell linear epitopes of HBeAg were identified, namely (1)MDIDPYKEFG(10), (37)LYREALESPEHCSP(50), (74)SNLEDPAS(81) and (127)RTPPAYRPPNAPIL(140). The rabbits immunized with the KLH conjugate showed an antibody titer over 1:512 000. The antisera of B-cell linear epitopes collected could specifically react with HBeAg as shown by ELISA.</p><p><b>CONCLUSION</b>Four B-cell linear epitopes of HBeAg have been confirmed using bioinformatics methods, which provides new evidence for further functional studies of HBeAg in hepatitis B.</p>

Preparation and activity detection of chicken egg yolk IgY antibody against human papillomavirus 16 type L1 main capsid protein / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare highly specific chicken egg yolk IgY antibody against human papillomavirus 16 type L1 main capsid protein (HPV16L1) for detection of HPV16L1.</p><p><b>METHODS</b>Purified HPV16L1 protein was used to immunize the hens, from which the eggs were collected since one week after the first immunization. The egg yolk was separated and the IgY antibody purified by PEG-6000 method. The bioactivity of the antibody was tested using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was performed to detect the HPV16L1 in the CHO cells transfected with the recombinant pcDNA-EGFP-HPV16L1 plasmid (containing EGFP-HPV16L1 fusion gene) for assessing the specific affinity of IgY to HPV16L1.</p><p><b>RESULTS</b>After 3 immunizations of the hens, the titer of the purified IgY antibody against HPV16L1 from the egg yolk reached 1:10240. The IgY bound specifically to the EGFP-HPV16L1 protein expressed in the transfected CHO cells.</p><p><b>CONCLUSION</b>High titer IgY can be prepared by immunization of the hens with HPV16L1 protein, and the prepared IgY can be used for HPV16L1 detection at the cellular level.</p>

Activity identification of peptide containing rat sodium pump α2 subunit M1-M2 extramembrane fragment in vitro / 生理学报

In order to explore the activity of a peptide containing rat sodium pump α2 subunit M1-M2 extramembrane fragment (RES2 derivative) in vitro, the peptide (Leu-Ala-Ala-Met-Glu-Asp-Glu-Pro-Ser-Asn-Asp-Asn-Gly-Gly-Gly-Ser) was synthesized by peptide synthesizer with Fmoc method and purified by high performance liquid chromatography (HPLC). Its binding activity was identified by radioligand-receptor binding assay (RRA) and its bioactivity was measured by erythrocyte (86)Rb uptake. The results of saturation binding experiment and competitive binding experiment showed that the synthesized RES2 derivative had the capability to bind to (3)H-ouabain. The dissociation constant (K(d)) was 38.46 nmol/L and IC(50) was 6.353 nmol/L. Erythrocyte (86)Rb uptake experiment showed that the RES2 derivative blocked the inhibitory effect of ouabain on the sodium pump on erythrocyte membrane in a dose-dependent manner. The results showed that the RES2 derivative is capable of binding to ouabain and improving the activity of sodium pump on erythrocyte membrane, suggesting that the RES2 derivative might become an effective antihypertensive drug in the future.

Preparation and application of anti-ouabain IgY antibody / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare highly specific anti-ouabain polyclonal antibody for detecting endogenous ouabain in tissues.</p><p><b>METHODS</b>Ouabain-BSA compound was used to immunize hens, and the eggs were collected one week after the first immunization. The IgY antibodies in the egg yolk were separated and purified by PEG-6000 Method, and analyzed by 12% SDS-PAGE and enzyme-linked immunosorbent assay (ELISA) for titration. The IgY antibodies obtained were applied subsequently in ELISA and immunohistochemistry.</p><p><b>RESULTS</b>The IgY titer increased rapidly after the second immunization, with the highest titer of 1:10240 that lasted for at least 4 weeks. Competitive ELISA for IgY detection showed an average intraassay coefficient of variation (CV) of 2.03% and an inter-assay CV of 2.34%. Immunohistochemistry visualized the location of the endogenous ouabain mainly in the cytoplasm of the zona reticularis of rat adrenal cortex.</p><p><b>CONCLUSION</b>Immunization of hens allows efficient preparation of IgY antibody which can be used in routine immunoassays.</p>

Comparison between anti-ouabain egg yolk(IgY) and rabbit antibody(IgG) in enzyme-linked immunosorbent assay / 中国应用生理学杂志

<p><b>AIM</b>To improve specificity and accuracy of endogenous ouabain measurement assay.</p><p><b>METHODS</b>Anti-ouabain polyclonal antibody egg yolk (IgY) and anti-ouabain rabbit antibody (IgG) were prepared respectively. In the presence of two kinds of antibody, then the specificity and accuracy of enzyme-linked immunosorbent assay (ELISA) were compared.</p><p><b>RESULTS</b>The ELISA, in the presence of IgY, provided a sensitivity of the average intraassay coefficient of variation(CV) was 2.03%, and the inter-assay CV was 2.34% respectively. In contrast, IgG were 2.83% and 3.29%. No significant interferences were observed with hydrocortisone and dexamethasone. There was 3.45% vs. 5.95%, 3.20% vs. 5.20% of crossreaction with cedilanid and digoxin.</p><p><b>CONCLUSION</b>The specificity and accuracy of ELISA, in which IgY was used, were more better than IgG.</p>

Comparative study on intestinal metaplasia in Barrett's esophagus, cardia and gastric antrum / 中华消化内镜杂志

Objective To compare the differences in mucin-histochemistry and etiology of Barrett's esophagus (BE) intestinal metaplasia (IM) , cardiac intestinal metaplasia (CIM) and gastric antrum intestinal metaplasia (GA-IM). Methods Alcian blue /periodic acid-schiff (AB/PAS) and high iron diamine / alcian blue (HID/AB) histochemical methods were used to classify IM in BE, cardia and gastric antrum, and IM were classified into three subtypes: complete small intestinal type (type Ⅰ ) , incomplete small intestinal type (type Ⅱ) and incomplete colonic type (type Ⅲ). Compared the prevalence of different subtypes of IM in above-mentioned sites, and investigated their relationships among the symptoms of gastroesophageal reflux disease (GERD) and Helicobacter pylori (Hp) infection. Results The prevalence of type Ⅲ IM in long-segment BE (LSBE) and short-segment BE (SSBE) is 75. 0% and 63. 3% respectively, it is significantly higher than that in CIM (23. 1% ) and GA-IM ( 17. 7% ) (P

Development and application of HT-1 tissue microarrayer / 西安交通大学学报(医学版)

Objective To design and develop a reliable,ease-to-use and cheap tissue microarryer for making tissue microarrays,and discuss its characteristics.Methods According to the facture procedure and principle of tissue microarray construction,HT-1 tissue microarrayer was designed and developed.The tissue microarrayer consisted of a recipient paraffin block molding machine,a punch needle,a negative-pressure embedding instrument,and a special manipulator.Using HT-1 tissue microarrayer,the array holes in recipient paraffin block could be punched by single-shaping technique in one action in several seconds,while no chapping was guaranteed.During the TMAs paraffin block embedding process,the remnant air bubble between the tissue cylinders and array holes in recipient paraffin block could be exhausted rapidly and completely.Results Using HT-1 tissue microarrayer,an array holes recipient paraffin block(several to several hundreds holes)could be made in several seconds.Several TMAs blocks with 56 tissue cylinders(1.5 mm in diameter)were constructed easily and quickly within 20 min.Under HE and immunostaining procedures,the tissue cores were well aligned,and orientation was properly done.The tissue cores on the slide maintained intact histological structure.The tissue structure and background of the HE and immunostaining were clear.There was less sample loss(the loss rate was less than 1.0%?1.1%).Conclusion HT-1 tissue microarrayer is a simple,economical and high efficiency/cost(E/C)and easy-to-use device.

The clinical and pathologic characteristics of gastrointestinal stromal tumor / 西安交通大学学报(医学版)

Objective To explore the clinical, pathologic and immunohistochemical characteristics of gastrointestinal stromal tumor (GIST) and stromal tumor beyond the gastrointestinal tract. Methods Expression of CD117, CD34, SMA, Desmin and S-100 protein in 53GIST were detected using immunohistochemical S-P method, and then analyzed. Results Of 53 cases, 38 cases were detected as spindle type, 6 as epithelioid type and 9 as mixture type; 9 cases were benign,20 were borderline and 24 were malignant. Of the 9 benign cases, 8 originated in stomach, while only one originated in intestine and beyond the gastrointestinal tract. The rate of immunohistochemical expression was showed as follows: CD117 92.45% and CD34 77.36%. Conclusion GIST has its unique morphological characteristics. To detect CD117 and CD34 simultaneously may be helpful to the diagnosis. The malignant potential of stromal tumor in intestine and beyond the gastrointestinal tract is higher than that in stomach. The estimation of benignancy and malignancy depends on the site, the size and nuclei mitoses of the tumor.