Understanding endometriosis from an immunomicroenvironmental perspective / 中华医学杂志(英文版)

Endometriosis, a heterogeneous, inflammatory, and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus, affects approximately 5-10% of reproductive-age women, causing chronic pelvic pain and reduced fertility. Although the etiology of endometriosis is still elusive, emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris. Peritoneal macrophages and natural killer (NK) cells exhibit deficient cytotoxicity in the endometriotic microenvironment, leading to inefficient eradication of refluxed endometrial fragments. In addition, the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation, which contribute to endometriosis development. Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis, therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression. Here, we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment, focusing on their interactions with microbiota and endocrine and nervous systems, and how these interactions contribute to the etiology and symptomology of endometriosis.

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats / 中华烧伤杂志

Objective: To investigate the effects and molecular mechanism of exogenous L-carnitine on hepatic pyroptosis mediated by excessive endoplasmic reticulum stress in severely scald rats. Methods: The experimental research method was adopted. According to the random number table (the same group method below), fifteen female Sprague Dawley rats aged 6-8 weeks were divided into sham-injury group, scald alone group, and scald+carnitine group (with 5 rats in each group), and full-thickness scald of 30% total body surface area were made on the back of rats in scald alone group and scald+carnitine group, and rats in scald+carnitine group were additionally given intraperitoneal injection of L-carnitine. At post injury hour (PIH) 72, The levels of aspartate aminotransferase (AST) and alanine dehydrogenase (ALT) of biochemical indicators of liver injury were detected by automatic biochemical analyzer with the sample number of 5. At PIH 72, liver tissue damage was detected by hematoxylin-eosin staining. At PIH 72, The mRNA levels of nucleotide-binding oligomerization domain-containing protein-like receptor family pyrin domain containing 3 (NLRP3), cysteine aspartic acid specific protease 1 (caspase-1), gasderminD (GSDMD), and interleukin 1β(IL-1β) in liver tissue as pyroptosis-related markers and glucose regulatory protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in liver tissue as endoplasmic reticulum stress-related markers were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue were detected by Western blotting, and the sample numbers were all 5. HepG2 cells as human liver cancer cells were divided into dimethyl sulfoxide (DMSO) group, 0.1 μmol/L tunicamycin (TM) group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group and were treated accordingly. After 24 h of culture, cell viability was detected by cell counting kit 8, and the intervention concentration of TM was screened, and the sample number was 5. HepG2 cells were divided into DMSO group, TM alone group, and TM+carnitine group, and treated accordingly. After 24 h of culture, the protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in cells were detected by Western blotting, and the sample numbers were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference-t test. Results: At PIH 72, the AST and ALT levels of serum in scald alone group were (640±22) and (157±8) U/L, which were significantly higher than (106±13) and (42±6) U/L in sham-injury group, respectively, with t values of -46.78 and -25.98, respectively, P<0.01. The AST and ALT levels of serum in scald+carnitine group were (519±50) and (121±10) U/L, which were significantly lower than those in scald alone group, respectively, with t values of 4.93 and 6.06, respectively, P<0.01. At PIH 72, the morphology of liver tissue of rats in sham-injury group were basically normal with no obvious inflammatory cell infiltration; compared with those in sham-injury group, the liver tissue of rats in scald alone group showed a large number of inflammatory cell infiltration and disturbed cell arrangement; compared with that in scald alone group, the liver tissue of rats in scald+carnitine group showed a small amount of inflammatory cell infiltration. At PIH 72, the mRNA expression on levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 34.42, 41.93, 30.17, and 15.68, respectively, P<0.01); the mRNA levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 34.40, 37.20, 19.95, and 7.88, respectively, P<0.01). At PIH 72, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 12.28, 26.92, 5.20, 10.02, and 24.78, respectively, P<0.01); compared with those in scald alone group, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald+carnitine group were significantly decreased (with t values of 10.99, 27.96, 12.69, 8.96, and 12.27, respectively, P<0.01). At PIH 72, the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 21.00 and 16.52, respectively, P<0.01), and the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 8.92 and 8.21, respectively, P<0.01); the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 22.50 and 14.29, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 14.29 and 5.33 respectively, P<0.01). After 24 h of culture, the cell survival rates of 0.1 μmol/L TM group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group were significantly decreased than that in DMSO group (with t values of 4.90, 9.35, 18.64, and 25.09, respectively, P<0.01). Then 0.8 μmol/L was selected as the intervention concentration of TM. After 24 h of culture, compared with that in DMSO group, the protein expression levels of GRP78 and CHOP in cells in TM alone group were significantly increased (with t values of 10.48 and 17.67, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in TM+carnitine group were significantly lower than those in TM alone group (with t values of 8.08 and 13.23, respectively, P<0.05 or P<0.01). After 24 h of culture, compared with those in DMSO group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM alone group were significantly increased (with t values of 13.44 and 27.51, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05); compared with that in TM alone group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM+carnitine group were significantly decreased (with t values of 20.49 and 21.95, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05). Conclusions: In severely scald rats, exogenous L-carnitine may play a protective role against liver injury by inhibiting the pathways related to excessive endoplasmic reticulum stress-mediated pyroptosis.

Analysis on Mechanism of Astragali Radix in Treating IgA Nephropathy Based on Network Pharmacology and in Vitro Cell Experiment / 中国实验方剂学杂志

Objective:To explore the multi-component， multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy （IgAN） by network pharmacology， aiming to provide evidence for its basic research and clinical application. Method:The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards， Traditinal Chinese Medicine Integrated Database （TCMID）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis， cell experiments <italic>in vitro</italic> were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53 （PI3K/Akt/p53） signaling pathway of human mesangial cells. Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items， which were related to nuclear hormone receptor binding， nuclear receptor activity， deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways， which were closely related to PI3K/Akt signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， advanced glycation end product/receptor of advanced glycation end product （AGE/RAGE） signaling pathway and others. Cell experiments <italic>in vitro </italic>confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB （PDGF-BB）-induced proliferation of human mesangial cells by regulating PI3K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis， oxidative stress， inflammation response and others， providing ideas and directions for the new drug development and mechanism study of IgAN.

Myricetin inhibits interferon-γ-induced programmed death ligand-1 and indoleamine 2, 3-dioxygenase 1 expression in lung cancer cells / 中国药理学与毒理学杂志

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

Identification of specific key Hub genes in young hepatocellular carcinoma patients based on bioinformatical analysis and its clinical significance / 中国肿瘤生物治疗杂志

@#Objective: To identify the specific Hub genes in young hepatocellular carcinoma (HCC) patients, and to explore their biological and clinical significance by using bioinformatic methods. Methods: The data information of HCC and normal tissues of young (≤40 years old at diagnosis) and old (＞40 years old at diagnosis) HCC patients were obtained from GEO chip data set GSE45267. The differentially expressed genes (DEGs) in HCC tissues as comparing to normal tissues in the two groups were screened by using GEO2R and Venn chart software. The Protein-Protein Interaction (PPI) network of the specific DEGs in young group was constructed by bioinformatics tools STRING and Cytoscape to screen the Hub genes and significant modules. The Hub genes were verified by GEPIA database, and the overall survival time was analyzed by Kaplan-Meier. Finally, Gene Ontology (GO) Enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the DEGs specific to young group and the common DEGs of the two groups by DAVID. Results: Finally, 117 up-regulated and 179 down-regulated DEGs specific to the young group were screened out, and PPI network screened 10 most connected genes as Hub genes, among which 7 Hub genes were concentrated in the first module. Six up-regulated Hub genes, including TYMS, CDC6, BUB1, TPX2, OIP5 and KIF23, were indicated to associate with the poor prognosis in young HCC patients by GEPIA and Kaplan-Meier analysis. GO function and KEGG pathway analyses showed that the DEGs specific to young HCC patients were mainly involved in biological processes such as ATP binding, and were mainly enriched in S phase of cell cycle; while the common DEGs of two groups were mainly involved in biological processes such as cyclooxygenase P450 and cell division, and were mainly enriched in the G2/M phase of the cell cycle. Conclusion: In this study, 6 up-regulated DEGs specific to young group that suggested poor prognosis were identified, which may be the potential therapeutic and prognostic targets for young patients with HCC.

Next-generation Sequencing Study of Pathogens in Serum from Patients with Febrile Jaundice in Sierra Leone / 生物医学与环境科学（英文）

OBJECTIVE@#People in Western Africa suffer greatly from febrile jaundice, which is caused by a variety of pathogens. However, yellow fever virus (YFV) is the only pathogen under surveillance in Sierra Leone owing to the undeveloped medical and public health system there. Most of the results of YFV identification are negative. Elucidation of the pathogen spectrum is required to reduce the prevalence of febrile jaundice.@*METHODS@#In the present study, we used Ion Torrent semiconductor sequencing to profile the pathogen spectrum in archived YFV-negative sera from 96 patients in Sierra Leone who presented with unexplained febrile jaundice.@*RESULTS@#The most frequently identified sequencing reads belonged to the following pathogens: cytomegalovirus (89.58%), Epstein-Barr virus (55.21%), hepatitis C virus (34.38%), rhinovirus (28.13%), hepatitis A virus (20.83%), coxsackievirus (10.42%), Ebola virus (8.33%), hepatitis E virus (8.33%), lyssavirus (4.17%), leptospirosis (4.17%), chikungunya virus (2.08%), Crimean-Congo hemorrhagic fever virus (1.04%), and hepatitis B virus (1.04%).@*CONCLUSION@#The distribution of sequencing reads suggests a broader spectrum of pathogens for consideration in clinical diagnostics and epidemiological surveillance in Sierra Leone.

Clinical significance of tumor infiltrating lymphocytes in high-grade serous ovarian carcinoma / 中华病理学杂志

Objective@#To compare intratumoral tumor-infiltrating lymphocytes (TIL) in a cohort of high-grade serous ovarian carcinoma patients between those who treated with neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS), and to determine the clinical and prognostic significance of TIL in high-grade serous ovarian carcinoma.@*Methods@#Tissue microarrays and immunohistochemistry were used to assess the quantity of CD3+, CD4+ and CD8+ lymphocytes in tumor tissue from 138 high-grade serous ovarian carcinoma (PDS n=84, NACT n=54) which were collected from January 2013 to January 2016 at West China Second University Hospital, Sichuan University. TIL was analysed in two predefined groups of low and high TIL. The associations between clinical features and TIL were evaluated by χ2 test or Fisher′s exact test, and Kaplan-Meier survival analysis and Cox proportional hazards regression model were used for the association between the amounts of TIL and progression free survival.@*Results@#There was no difference in TIL/HPF (high-power field) counting in tumor tissue between PDS and NACT (P>0.05), and in the PDS cohort, CD3+, CD4+ and CD8+TIL were not associated with any clinical features like age, FIGO stage, tumor size and chemotherapy sensitivity, however, in the NACT cohort, CD8+TIL was strongly associated with chemotherapy sensitivity. The univariable analysis supported that high CD8+TIL in tumor tissue was associated with longer progression free survival both in the PDS and NACT cohort(P=0.030, P=0.032), but not CD4+TIL, in the NACT cohort, high CD3+TIL were also associated with longer progression free survival (P=0.019). Finally, in multivariate analysis, only the high CD8+TIL had prognostic significance (HR=0.369, 95%CI=0.176-0.772, P=0.008).@*Conclusion@#High CD8+lymphocytes density in tumor tissue was significantly associated with improved progression free survival in high-grade serous ovarian carcinoma. Besides, the CD8+lymphocytes density could be served as a potential marker of the chemotherapy sensitivity in patients who treated with neoadjuvant chemotherapy.

Three-dimensional ultrasonic virtual organ computer-aided analysis with different angels in evaluation of fetal gallbladder volume / 中国医学影像技术

Objective To investigate the consistency of fetal gallbladder volume (FGV) during middle-late pregnancy with three-dimensional ultrasonic virtual organ computer-aided analysis (VOCAL) technique at different rotation angles,and to analyze the correlation between FGV and gestation age.Methods A total of 157 healthy pregnant women underwent prenatal screening were included.The reference range of FGV was measured with three-dimensional ultrasonic VOCAL at 30°,18° and 12° rotation angle,respectively.The correlation between FGV and gestation age was observed,and the consistency of FGV values measured with VOCAL at different rotation step angles was compared.Results The correlations between FGV values measured with VOCAL at 30°,18°,12° rotation step angles and gestation age were all excellent (r=0.92,0.88,0.90;all P＜ 0.001).The consistency of FGV values measured with VOCAL at different rotation step angles was very good (30° and 18°,ICC=0.94;30° and 12°,ICC=0.97;18° and 12°,ICC=0.94).Conclusion Three-dimensional ultrasonic VOCAL can be used to establish the reference range of fetal gallbladder volume in middle-late pregnancy.The consistency of FGV values measured with VOCAL at different rotation step angles was very good,and the correlation between FGV and gestation age was excellent.

Dispersion degree of a small-dose bone cement / 中国组织工程研究

BACKGROUND:During the percutaneous vertebroplasty, the optimal dose of bone cement that can bring favorable cement dispersion and remodel the biomechanical balance of the fractured vertebrae remains controversial. OBJECTIVE:To investigate the dispersion degree of small dose of bone cement in vertebroplasty. METHODS: In this experiment, 18 sheep selected with the same condition were randomly divided into three groups (group A, group B, group C), 6 in each group. A model of thoracolumbar vertebral compression fracture (T12, L1, L2) was made in each sheep. The injected volume of bone cement in groups A, B, C was 15％, 20％, 25％ of the average volume of adjacent vertebral bodies, respectively. Postoperative CT images were used to evaluate the bone cement dispersion. Dispersion degree of bone cement among the three groups was compared by the Kruskal-Wallis test. RESULTS AND CONCLUSION:There was no statistical difference in the dispersion degree of bone cement among the three groups, and the excellent and good rate of dispersion was over 80％. To conclude, the optimal dose of bone cement injected into the fractured vertebra is 15％ of the average volume of adjacent vertebral bodies, which can achieve good dispersion degree and restore the biomechanical stability of the vertebral body.

Epidemiologic Study of Adult Femoral Head Osteonecrosis in Chengdu, China / 中国康复理论与实践

@#Objective To investigate the morbidity and characteristics of adult osteonecrosis of the femoral head (ONFH) in Chengdu, and to further explore its related risk factors.Methods Self-designed questionnaires were used to collect data by the way of household or field survey. From January,2016 to February, 2018, a total of 544 cases (797 hips) diagnosed as ONFH were included in the study. The medical data including general condition, risk factors, diagnosis, disease stages and treatment were collected. Based on the data, the risk factors were analyzed statistically.Results The average age of 544 patients (392 males and 152 females) was 55 years old (range: 19 to 90 years); the bilateral incidence was 46.51% (253 cases). The proportion of Association Research Circulation Osseous stages was accounted respectively 3.64% for stage I, 6.15% for stage II, 8.41% for stage III and 81.81% for stage IV when confirmed ONFH initially. In all the reasons of ONFH, 52.39% were alcohol-associated osteonecrosis, 16.18% for steroid-induced osteonecrosis, 11.58% for traumatic osteonecrosis, 5.88% for dysplastic osteonecrosis, and 13.97% for other reasons.Conclusion The incidence of ONFH was higher in men than in women. Stages III-IV accounted for the highest proportion. The high intake of alcohol or overuse of steroid was the leading causes of adult ONFH, among which alcohol-associated osteonecrosis was the main for the males and steroid-induced osteonecrosis for the females.

A Study on the Practicability and Influencing Factors of the Frailty Assessment in Elderly Patients with Coronary Atherosclerotic Heart Disease / 现代生物医学进展

Objective:To investigate the correlation and influence factors of three weak assessment scales in the evaluation of debilitating condition of elderly patients with coronary heart disease (CHD).Methods:120 cases with CHD in our hospital were chosen,the clinical material were collected.The Fried weak score,clinical weak score and EFS were assessed.The correlation of three weak assessment scales were analyzed.Results:Fried score,CFS score and EFS score determined 6 cases,8 cases and 14 cases patients with weak respectively,the incidence rate were 5.0％,6.7％ and 11.7％,which had no significant difference(P＞0.05).The linear correlation analysis indicated the Fried score,CFS score and EFS score had positive correlation(P＜0.05),which had consistency with CHD patients.The CFS score and EFS score had no significant correlation (P＞0.05).Cox regression analysis showed that the cultural level and grade of cardiac function,living conditions and sleep disorders were influencing factors of Fried scores(P＜0.05).Conclusion:Three weak assessment had consistence and different clinical value for the evaluation of weakness in CHD patients,the cultural level and grade of cardiac function,living conditions and sleep disorders were influencing factors of weakness in CHD patients.

Comparison of 99mTc-MIBI SPECT/CT and ultrasonography in diagnosis of hyperparathyroidism / 上海交通大学学报（医学版）

Objective·To explore the diagnostic value of 9 mTc-sestamibi (9 mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) and ultrasonography in hyperparathyroidism. Methods·Fifty patients with hyperparathyroidism were included. 9 mTc-MIBI SPECT/CT was performed before operations in all patients, while ultrasonography was performed in 33 patients. The diagnostic efficiency was calculated for both imaging methods in comparison to pathological data. Results·Serum parathyroid hormone (PTH) levels were 352.0 (141.5-846.0) pg/mL and 1792.0 (1018.5-2358.5) pg/mL, respectively, in primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT), while maximum diameters of lesion were 14.5 (9.0-20.9) mm and 10.0 (8.0-12.6) mm, respectively (both P<0.01). The accuracy of SPECT/CT were 97.7% and 62.5%, respectively (P<0.01), in PHPT and SHPT. In 33 patients, the sensitivity and accuracy of SPECT/CT were 66.3% and 74.2%, respectively, whereas the sensitivity and accuracy of ultrasonography were 45.7% and 61.4%, respectively (both P<0.05). Conclusion·Serum PTH levels were higher, while maximum diameters of lesion were longer in PHPT than that in SHPT, and the diagnostic efficiency was also higher in PHPT than that in SHPT. In the other hand, the sensitivity and accuracy of SPECT/CT were higher than that of ultrasonography.

Current Application Status of Artery Access in Percutaneous Coronary Intervention and Their Impact on Long-term Prognosis in Relevant Patients: A single Center Experience in 10577 Patients / 中国循环杂志

Objective: To explore the application status of trans-femoral route (TFR) and trans-radial route (TRR) percutaneous coronary intervention (PCI) via a single center large sample 2-year follow-up study and to evaluate their impact on long-term prognosis in relevant patients. Methods: A total of 10577 patients received PCI by TFR or TRR in our hospital during 2013 were analyzed. The patients were divided into two groups: TRR group, n=9745 (90.9％) and the TFR group, n=812 (7.6％). Clinical features were compared between 2 groups and their impacts on prognosis were studied. Results: Compared with TRR group, TFR group had more patients with elder age, more female, diabetes, more with the histories of myocardial infarction (MI), PCI or CABG, all P<0.001; more patients with left main disease or 3-vessel lesions, all P<0.001. Logistic regression analysis indicated that female, age, histories of MI, PCI or CABG and left main disease were the predictors for choosing TFR. With propensity score matching, TFR group had the higher in-hospital mortality than TRR group, P<0.05. 2-year follow-up Kaplan-Meier survival analysis showed that the end point events were similar between 2 groups. Cox multivariate analysis found that TFR was an independent risk factor of BARC ≥ 2 bleeding (HR=2.210, P=0.013), while not an independent risk factor for main cardiac end point events. Conclusion: ① Female, elder age, histories of MI, PCI or CABG and left main disease were the predictors for choosing TFR. ② The in-hospital mortality was higher in TFR PCI. ③ TFR was an independent risk factor of BARC≥2 bleeding, while it had no impact on long-term prognosis in PCI patients.

Current Application Status of Artery Access in Percutaneous Coronary Intervention and Their Impact on Long-term Prognosis in Relevant Patients: A single Center Experience in 10577 Patients / 中国循环杂志

Objective: To explore the application status of trans-femoral route (TFR) and trans-radial route (TRR) percutaneous coronary intervention (PCI) via a single center large sample 2-year follow-up study and to evaluate their impact on long-term prognosis in relevant patients. Methods: A total of 10577 patients received PCI by TFR or TRR in our hospital during 2013 were analyzed. The patients were divided into two groups: TRR group, n=9745 (90.9％) and the TFR group, n=812 (7.6％). Clinical features were compared between 2 groups and their impacts on prognosis were studied. Results: Compared with TRR group, TFR group had more patients with elder age, more female, diabetes, more with the histories of myocardial infarction (MI), PCI or CABG, all P<0.001; more patients with left main disease or 3-vessel lesions, all P<0.001. Logistic regression analysis indicated that female, age, histories of MI, PCI or CABG and left main disease were the predictors for choosing TFR. With propensity score matching, TFR group had the higher in-hospital mortality than TRR group, P<0.05. 2-year follow-up Kaplan-Meier survival analysis showed that the end point events were similar between 2 groups. Cox multivariate analysis found that TFR was an independent risk factor of BARC ≥ 2 bleeding (HR=2.210, P=0.013), while not an independent risk factor for main cardiac end point events. Conclusion: ① Female, elder age, histories of MI, PCI or CABG and left main disease were the predictors for choosing TFR. ② The in-hospital mortality was higher in TFR PCI. ③ TFR was an independent risk factor of BARC≥2 bleeding, while it had no impact on long-term prognosis in PCI patients.

Formula Optimization and Quality Control of Amlexanox Nasal Thermosensitive Gel Spray / 中国药师

Objective:To optimize the formula of amlexanox nasal thermosensitive gel spray and establish the quality control meth-od. Methods:Amlexanox nasal thermosensitive gel spray was prepared by a cold dissolving method, and poloxamer 407 (P407) and poloxamer 188 (P188) were used as the carrier materials. Central composite design-response surface methodology was used to optimize the formula with the amount of P407 and P188 as the influencing factors and the gel temperature and the viscosity before gelling as the indices. The content of amlexanox was determined by HPLC. According to Chinese Pharmacopoeia (2010 edition), the other indices of the preparation such as appearance, pH, viscosity, content, total spray times of each bottle and the content of each spray were deter-mined as well. Results:The optimum ratio of P407 and P188 was 17. 0% and 0. 9%,respectively . The average recovery of amlexanox was 98. 8% and RSD was 1. 7%(n=9). The quality of 3 batches of amlexanox nasal thermosensitive gel spray met the related require-ments. Conclusion:The formula and preparation process of amlexanox nasal thermosensitive gel spray are reasonable and feasible with controllable quality, which is worthy of further research.

Effects of Three Herb Extracts on Cell Proliferation and Collagen Synthesis in Cultured Human Dermal Fi-broblasts / 中国药师

Objective:To investigate the effects of three herb extracts on cell proliferation and collagen synthesis in cultured hu-man dermal fibroblasts. Methods:The human dermal fibroblasts were isolated and cultured with tissue explant culture technique. Im-munohistochemical staining was performed to observe vimentin in fibroblasts. The proliferation of fibroblasts was determined by MTT as-say. Hydroxyproline in the cultural medium was determined by a digestion method. Results:The cells were typical fibroblasts, and the immunohistochemistry staining of vimentin in the cells was positive. The three herb extracts could promote the proliferation of the fibro-blasts at appropriate concentrations in a time-dependent manner. After the 72-hour culture in the medium, 0. 312 5-5. 000 0 mg·ml-1 Aloe vera gel extract, 0. 156 3-2. 500 0 mg·ml-1 Bletilla striata extract and 0. 075 0 mg·ml-1 salvianolate showed significant effects on the proliferation of fibroblasts (P<0. 05 or P<0. 01 vs the blank group). Compared with that in the blank group, the amount of hydroxyproline in the three herb extracts cultural medium was also increased (P<0. 05 or P<0. 01). The effect of salvianolate on the cell proliferation was closely related with time and concentration, and the high concentration group could inhibit the growth of fibroblasts as the extension of time. Conclusion:Aloe vera gel extract, bletilla striata extract and salvianolate can promote the proliferation of fi-broblasts and the production of hydroxyproline, which may contribute to the wound healing.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma / 中国医学科学杂志(英文版)

<strong>Objective</strong> To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. <strong>Methods</strong> uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. <strong>Results</strong> uPAR level in bone marrow fluid of MM patients (1.52±0.32 μg/ml) was found to be higher than that in the control group (0.98±0.15 μg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. <strong>Conclusion</strong> Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma / 中国医学科学杂志(英文版)

Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. Methods uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively. The distribution of uPAR in MM cells was examined using immunofluorescence staining. The pathological changes in different stages of MM patients were studied by HE staining. Results uPAR level in bone marrow fluid of MM patients (1.52±0.32 μg/ml) was found to be higher than that in the control group (0.98±0.15 μg/ml). Interestingly, uPAR protein (0.686±0.075 vs. 0.372±0.043, P<0.05) and mRNA (2.51±0.46 vs. 4.46±1.15, P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage. The expression of uPAR in MM bone marrow was confirmed by immunofluorescence staining. Moreover, HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma. Conclusion Our study reveals that uPAR expression is positively correlated with the development and progress of MM.

Formula Optimization of Ropivacaine Hydrochloride Transdermal Gel / 中国药师

Objective:To optimize the formula of ropivacaine hydrochloride transdermal gel. Methods:The steady transdermal rate and cumulative transdermal percentage in 24 h of ropivacaine hydrochloride gel were used as the indices, an orthogonal design was applied to select the optimal formula, and Design Expert 8. 0. 5. 0 software was used to analyze the results. Results: The optimal formula con-tained 2% carbomer, 10% propylene-glycol and 5% Azone. The steady transdermal rate of the optimal formula was 0. 6951 mg·h-1 · cm-2 . The cumulative transdermal percentage in 24 h of the optimal formula was 91. 04%, which was 22. 79% higher than that of ropiva-caine hydrochloride solution with the same concentration. Design Expert 8. 0. 5. 0 software could predict the steady transdermal rate and cumulative transdermal percentage in 24 h of the optimal formula. Conclusion: The preparation design is reasonable, and the gel has promising properties, which is suitable for skin local application.