Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer / 中华肿瘤杂志

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 μm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

Survey on knowledge, attitude and practice for diabetic retinopathy among diabetic patients in Shanghai suburb and related influencing factors / 中华全科医师杂志

Objective:To survey the knowledge,attitude and practice (KAP) for diabetic retinopathy (DR) among diabetic patients in Shanghai suburb, and to analyze the related influencing factors.Methods:A cross-sectional survey on KAP for diabetic retinopathy was conducted from January to January 2022,a total of 260 diabetic patients were selected from Huacao Town of Shanghai Minhang District by stratified cluster random sampling method as the investigation subjects. The gender, age, height, weight, education level, occupation, frequency of exercise or outdoor sports, medical insurance status, comorbid chronic diseases, diabetic retinopathy in direct relatives were documented;the KAP of diabetes retinopathy prevention and treatment was investigated by a self-designed questionnaire. The influencing factors were analyzed by univariate and multivariate regression analysis.Results:A total of 260 valid questionnaires were received with a recovery rate of 100.0%. The survey showed that the knowledge awareness rate, attitude positive rate and behavior execution rate were 25.38% (66/260), 50.76% (132/260) and 14.61% (38/260), respectively; scores of knowledge,attitude,behavior and medication compliance of the subjects were 13.74±4.55, 10.40±3.23 and 14.92±4.51, respectively. Univariate analysis showed that the knowledge was significantly related to occupations,frequency of exercise or outdoor exercise,chronic disease, direct relatives with DR( F=5.03, 8.77, 5.08, 32.37,all P<0.05);the attitude was significantly related to age, education level, chronic disease, direct relatives with DR and awareness level of DR( F=2.12, 2.09, 2.75, 3.28,all P<0.05); the behavior was significantly related to age, frequency of exercise or outdoor exercise, direct relatives with DR( F=2.30, 2.70, 3.11,all P<0.05). Multiple stepwise linear regression analysis showed that the knowledge awareness score was significantly associated with age,education levels,direct relatives with DR( t=2.83, 2.46, 6.24,all P<0.05),and the age, chronic disease, awareness score were significantly associated with the attitude toward DR prevention and treatment ( t=3.70, 3.42, 6.03,all P<0.05).Patients with insufficient awareness had worse behavior of DR prevention and treatment( t=11.00, P<0.05). Conclusions:The KAP status of DR prevention and treatment in diabetes patients in Huacao Town is less satisfactory. In order to prevent the occurrence of diabetic retinopathy, it is necessary to strengthen health education, improve self-management ability, enhance lifestyle intervention, and increase the frequency of exercise or outdoor exercise in diabetic patients.

Effect of Mankuining Decoction on Expression of Inflammatory Factors and Intestinal Flora in Mice with Ulcerative Colitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect and the possible mechanism of Mankuining decoction on dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） in mice. MethodA total of 90 male SPF C57BL/6 mice were randomly classified into normal group， model group， mesalazine group （0.266 g·kg-1）， and high-， and medium-， low-dose （20， 10， 5 g·kg-1） Mankuining decoction groups， with 15 rats in each group. Mice， except the normal group， drank 3% DSS solution for 7 days to induce UC， and administration （ig） started on the day of modeling. The model group and the normal group were given equivalent amount of 0.9% normal saline once a day for 7 days. The general conditions of mice were recorded every day and the disease activity index （DAI） was calculated. On the 8th day， mice were killed by cervical dislocation. All the colons and feces were collected. The length of colon was recorded， and the histopathological changes of colon were observed based on hematoxylin-eosin （HE） staining. The content of inflammatory factors in colon was detected by enzyme-linked immunosorbent assay （ELISA）， and the changes of intestinal flora in mouse feces were determined based on 16SrRNA sequencing. ResultCompared with the normal group， the model group had severe colon damage， reduction in colon length （P<0.01）， increase in DAI （P<0.01）， decrease in interleukin-10 （IL-10） and transforming growth factor-β1 （TGF-β1） in colon（P<0.01）， rise of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-17α （IL-17α）， and tumor necrosis factor-α （TNF-α） in colon （P<0.05， P<0.01）， and decrease in abundance and diversity of intestinal flora. Compared with the model group， mesalazine and high-， medium-， low-dose Mankuining decoction alleviated the colon injury， recovered the length of colon （P<0.01）， decreased DAI （P<0.01）， increased IL-10 and TGF-β1 in colon （P<0.01）， and decreased IL-1β， IL-6， IL-17α， and TNF-α in colon （P<0.01）. Moreover， they raised the abundance and diversity of intestinal flora compared with the model group， as manifested by the increase in the abundance of Firmicutes， Akkermansia， Dubosiella， and Blautia and the decrease in the abundance of Bacteroidetes， Muribaculaceae， Clostridia_UCG-014， and Alistipes. ConclusionMankuining decoction has definite effect in treating UC mice， and the effect is positively correlated with the concentration. In addition， different concentration has different influence on the structure of flora. The mechanism is the likelihood that it alleviates the disorder of intestinal flora to restore intestinal immune balance and further promote the recovery of colonic mucosa.

Hyperbaric oxygen treatment on keloid tumor immune gene expression / 中华医学杂志(英文版)

BACKGROUND@#Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work.@*METHODS@#From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC).@*RESULTS@#Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M (ITGAM), interleukin (IL)-4, IL-6, IL-2, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), CD86, transforming growth factor (TGF), CD80, CTLA4, and IL-10. CD80, ITGAM, IL-4, and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification.@*CONCLUSION@#HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4+T, might be the key regulatory immune cell, and its related gene expression needs further study.

Biopharmaceutical classification and transport mechanism of 4 alkaloids in Mongolian herbal medicine Sophorae Flavescentis Radix / 中国中药杂志

In this study, we studied the solubility and permeability of matrine, oxymatrine, sophoridine, and oxysophocarpine, four alkaloids in the Mongolian herbal medicine Sophorae Flavescentis Radix, and evaluated the absorption mechanism with the Caco-2 cell model, so as to provide a basis for the new drug development and efficacy evaluation of Sophorae Flavescentis Radix. The results showed that all the four alkaloids had high solubility and high permeability and can be well absorbed, belonging to the class-I drugs of Biopharmaceutical Classification System(BCS). The absorption(AP→BL) and excretion(BL→AP) of matrine and oxymatrine were not affected by the concentration while the absorption depended on P-gp protein. The absorption(AP→BL) and excretion(BL→AP) of sophoridine and oxysophocarpine were positively related to the concentration and time, and the absorption process was independent from P-gp protein. The results provide scientific reference and an experimental basis for the development of Mongolian medical prescriptions containing Sophorae Flavescentis Radix.

Anatomy of the gluteal region and its implication in liposculpture / 中华整形外科杂志

Objective@#To study the morphological characteristics and important anatomical structures of each soft tissue layer of gluteal region, and discuss the recommended levels and safe areas for liposculpture in this region.@*Methods@#Twenty-eight specimens of unilateral buttocks from 14 adult cadavers, including 16 specimens of unilateral buttocks from 8 fresh cadavers and 12 specimens from 6 formaldehyde fixed cadavers were dissected. Among the cadavers, there were 2 males with an average age of 49 years, and 12 females from 23 to 72 years old, median age 46 years. Through anatomy study of soft tissue layers of gluteal region, the morphological features of each layer were observed and documented, and the characteristics of fascia system and adipose tissue, as well as the relationship between the blood vessels and nerves with corresponding layers.@*Results@#The layers of the gluteal region that range from superficial to deep are skin, subcutaneous fat, superficial fascia system, deep fascia system, muscle and fascia compartments. Subcutaneous fat is distributed in superficial and deep layers; the superficial fascia system is well developed and dense with a layered structure; the deep fascia is thin with the characteristic of epimysium. There is a danger zone for deep fat graft in the gluteal region, with its apex at the first sacral vertebra, and its base goes along the gluteal fold, compromising the thighs′ medial two-thirds. Nearly all important blood vessels and nerves of gluteal region are located in deep layer of this danger zone.@*Conclusions@#Based on the characteristics of buttocks of Chinese people, liposuction is mainly performed in the iliolumbar region and posterolateral thigh, which can significantly increase the relative height and fullness of buttocks. For full buttocks, deep fat can be sucked appropriately, which should be longitudinal and gentle to reduce the damage to the superficial fascial system. There is a high risk for fat graft in the buttock. It is recommended to use a blunt needle with an inner diameter of more than 3 mm parallel to the fiber orientation of gluteus maximus for uniform fan-shaped injection with needle withdrawal. Satisfactory result can be obtained by injecting most fat into the subcutaneous adipose layer. Deep injection of grafts into dangerzoneis forbidden.

DestructionandProtectionStrategyofBlood-brainBarrierDuringIschemicStroke / 中山大学学报(医学科学版)

@#Blood-brainbarrier（BBB），abarrierstructurebasedonbrainmicrovascularendothelialcells，playsan importantroleinmaintainingthehomeostaticmicroenvironmentofcentralnervoussystem（CNS）.Underthepathological conditionsofischemicstroke，localinflammationandchangesinthestatusandstructureofcellsleadtoBBBdisruption. AsaresultofBBBpermeabilityrising，variousbloodcomponents，especiallyactivatedinflammatorycellsorinflammatory factors，passthroughthedamagedBBBtoreachcerebralinfarctionareaandaggravatebraininjury.Thisarticlereviews themechanismofBBBdisruptionbythefunctionofactivatedcellsclusteredininfarctionareaafterischemicstrokeand brieflysummarizesourteam′scurrentworkonrepairingBBBinjuries.

Headphone Evaluation for App-Based Automated Mobile Hearing Screening

Abstract Introduction With the need for hearing screenings increasing across multiple populations, a need for automated options has been identified. This research seeks to evaluate the hardware requirements for automated hearing screenings using a mobile application. Objective Evaluation of headphone hardware for use with an app-based mobile screening application. Methods For the purposes of this study, hEAR, a Bekesy-based mobile application designed by the research team, was compared with pure tone audiometric tests administered by an audiologist. Both hEAR and the audiologist's test used 7 frequencies (125 Hz, 250 Hz, 500 Hz, 1,000 Hz, 2000 Hz, 4,000 Hz and 8,000 Hz) adopting four different sets of commercially available headphones. The frequencies were regarded as the independent variable, whereas the sound pressure level (in decibels) was the dependent variable. Thirty participants from a university in Texas were recruited and randomly assigned to one of two groups, whose only difference was the order in which the tests were performed. Data were analyzed using a generalized estimating equation model at α = 0.05. Results Findings showed that, when used to collect data with the mobile app, both the Pioneer HDJ-2000 (Pioneer, Bunkyo, Tokyo, Japan) (p> 0.05) and the Sennheiser HD280 Pro (Sennheiser, Wedemark, Hanover, Germany) (p> 0.05) headphones presented results that were not statistically different from the audiologist's data across all test frequencies. Analyses indicated that both headphones had decreased detection probability at 4kHz and 8kHz, but the differences were not statistically significant. Conclusion Data indicate that a mobile application, when paired with appropriate headphones, is capable of reproducing audiologist-quality data.

Preparation and in vitro performance evaluation of doxorubicin loaded lipid calcium phosphate nanoparticles with shell-core structure / 药学学报

As an important drug carrier, liposome has the advantages of high biocompatibility and low immunogenicity. It has been widely used in the field of drug delivery, especially the targeted treatment of tumors. However, traditional liposomes are composed of flowing dynamic phospholipid membranes, which are easy to fuse together, resulting in aggregation and drug leakage. In addition, the lower degree of polyethylene glycol (PEG) modification also limits the targeted delivery performance of the vector in vivo. In view of the problems, a nanoparticle-targeted drug delivery system combining the inorganic carrier calcium phosphate with liposomes was designed, namely lipid calcium phosphate (LCP). Using doxorubicin (DOX) as a model drug, doxorubicin-loaded lipid calcium phosphate nanoparticles (DOX/LCP) were prepared by reverse microemulsion method, and the preparation conditions were investigated. The structure and morphology of calcium phosphate cores were observed by infrared spectroscopy, EDS spectroscopy, and transmission electron microscopy. The particle size, encapsulation efficiency, drug loading, stability and release behavior in vitro of DOX/LCP were investigated. Confocal microscopy and flow cytometry were used to qualitatively and quantitatively evaluate the uptake of DOX in drug-resistant tumor cell line MCF-7/DOX by LCP, respectively, and the thiazolium MTT colorimetric method was used to examine its cytotoxicity. LCP exhibited a typical core-shell structure with good size uniformity and dispersibility. The particle size was in (48.6 ±3.9) nm, the potential was in (−12.1 ±1.2) mV, and the encapsulation efficiency was above 80%. Moreover, it has a good stability in simulated plasma. In vitro release of LCP had a significant pH dependence. When the pH of the environment was 7.4, the cumulative release within 24 hours was less than 20%; as the pH of the release medium decreases, the release rate of DOX/LCP was accelerated gradually. Accumulated release over 24 hours exceeded 90% in the pH 4.5 medium. LCP significantly promoted the uptake and accumulation of DOX by drug-resistant cells, and the inhibition rate of drug-resistant tumors was significantly increased in vitro. The half maximal inhibitory concentrations (IC50) of LCP/DOX and free DOX were 4.6 and 11.8 μg·mL−1, respectively, and there was a significant difference between the two groups (P < 0.05). In summary, the LCP prepared in this study had a small particle size, high encapsulation efficiency and good stability. It had environmental responsiveness and potential inhibition of tumor drug resistance, which suggests a potential in the clinical application.

Transplantation of umbilical cord blood mesenchymal stem cells at two states:comparison of neurological function recovery in cerebral infarction rats / 中国组织工程研究

BACKGROUND: Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) can repair the injury of nerve cells caused by ischemia and hypoxia, but which state of cells has a better therapeutic efficacy, primary isolation or induced differentiation is not yet known. OBJECTIVE: To compare the therapeutic effects of hUC-MSCs primary cultured and differentiated in a rat model of cerebral infarction.METHODS: After full-term delivery, fetal umbilical cord blood samples were obtained using quadruple bags by means of density gradient centrifugation. hUC-MSCS were induced in the medium containing basic fibroblast growth factor. Sixty rats were equivalently randomized into four groups: sham, model, primary culture and induced differentiation groups. Animal models of cerebral infarction were made in the rats in the latter three groups. Model rats in the primary culture and induced differentiation groups were subjected to tail vein transplantation of hUC-MSCs that were primary cultured or induced to differentiate in vitro at 7 days after modeling. RESULTS AND CONCLUSION: A marked improvement in balance, walking, spatial orientation, and learning and memory abilities was found in the rats after transplantation of hUC-MSCs that were primary cultured or induced to differentiate. Moreover, compared with the primary culture group, a significant improvement was found in the induced differentiation group, including improved pathological injury of the brain, higher expression of CD34 and Ki-67, lower expression of glial fibrillary acidic protein, lower expression of interleukin 1β and tumor necrosis factor β. Compared with the primary culture group, similar infarction size and expression of interleukin-6 were also found in the induced differentiation group. These findings indicate that hUC-MSCs with induced differentiation exhibit better therapeutic outcomes in the recovery of neurological function of cerebral infarction rats.

Knowledge-attitude-practice of chronic kidney disease among type 2 diabetic patients in a township of Shanghai suburb / 中华全科医师杂志

A total of 510 patients with type 2 diabetics mellitus (T2DM)from Huacao Township of Shanghai suburb were enrolled in the study. The gender, age, duration for diabetes, HbA1c level, blood pressure level, obesity status and health education of chronic kidney disease (CKD) were recorded. The knowledge, attitude and practice (AKP) of the subjects regarding prevention and treatment of CKD were assessed by using a self-restraint questionnaire. The data were analyzed with logistic regression. The knowledge awareness rate, attitude positive rate and behavior execution rate were 44.1％(225/510), 49.0％(250/510) and 16.5％(84/510), respectively. Scores of knowledge,attitude,behavior and medication compliance of the subjects were 16.8 ± 4.8, 18.3 ± 3.6 and 13.1 ± 4.1, respectively. The attitudes were closely related to educational level, HbA1c level, systolic blood pressure, obesity, health education history, and awareness level of CKD;behaviors were closely related to education level, systolic blood pressure, obesity, health education history and CKD prevention and treatment(P<0.05).

Management of patients with chronic kidney disease in the community / 中华全科医师杂志

Huacao Community Health Service Center has established an integrated chronic kidney disease (CKD) management system since 2015,which greatly improved CKD management in the community.From September 2016 to August 2017,4084 residents were screened by the family doctor team,975 were suspected to have CKD (23.87％),among whom 202 (20.72％) were referred to district CKD treatment center,and 197 (97.52％) were confirmed as CKD.The detection rate of suspected CKD among patients with hypertension and diabetes mellitus was the highest,which was much higher than that among outpatients and those with routine health check up.It is suggested that the integrated management of CKD should be widely implemented to cope with the prevalence of CKD,particularly for those with hypertension and diabetes.

5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer / 基因组蛋白质组与生物信息学报·英文版

Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E-19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient's cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.

Inhibitory effect of apatinib on HCT-116 cells and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved.</p><p><b>METHODS</b>The cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting.</p><p><b>RESULTS</b>Apatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an ICvalue of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes.</p><p><b>CONCLUSION</b>Apatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.</p>

Absorption enhancing effects and safety of PAMAM dendrimers on liquiritin / 中国中药杂志

PAMAM dendrimer is one of the most widely studied dendrimers in recent years, which has a large number of functional groups on the surface and cavities inside, specific three-dimensional structure and good biocompatibility, permeability and stability. It has been widely applied in drug and gene carrier fields and may become a new absorption enhancer. In order to study the absorption enhancing effects of PAMAM dendrimers, liquiritin was selected as the model drug, with the protection of spleen and liver, detoxification and other functions, but it had not been widely used in clinical application because of its difficult absorption, first pass effect, and low bioavailability. This topic was based on the two main determinants (solubility and permeability) of intestinal absorption in the body, researched the physicochemical properties of liquiritin, analyzed the transport volume of liquiritin with or without PAMAM dendrimers by using Caco-2 cell model, and analyzed the cytotoxicity of PAMAM dendrimers on Caco-2 cells by MTT experiments. These results showed that 0.1% of the G4 generation PAG can promote the absorption of liquiritin safely and effectively, and it was suitable for further development into a new type of pharmaceutical excipients.

Mechanism of Dynamic Near-infrared Fluorescence Cholangiography of Extrahepatic Bile Ducts and Applications in Detecting Bile Duct Injuries Using Indocyanine Green in Animal Models / 华中科技大学学报（医学）（英德文版）

Fluorescence intraoperative cholangiography (IOC) is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green (ICG).However,the dynamic process and mechanism of fluorescenceIOC have not been elucidated in previous publications.Herein,the optical properties of the complex of ICG and bile,dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated.The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration.Extrahepatic bile ducts could fluoresce 2 min after intravenous injection,and the fluorescence intensity reached a peak at 8 min.Inaddition,biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum.Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein.Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells,excretion of ICG into the bile and then its interaction with protein molecules in the bile.Moreover,fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models.All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.

Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment.</p><p><b>METHODS</b>Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture.</p><p><b>RESULTS</b>Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 μg/ml: t = -0.894, P = 0.397; 10 μg/ml: t = -3.348, P = 0.019; 20 μg/ml: t = -7.639, P < 0.001).</p><p><b>CONCLUSIONS</b>This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.</p>

Biopharmaceutics classification and absorption mechanisms primary study on four kinds of flavonoids / 中国中药杂志

The solubility and permeability on four kinds of flavonoids (kaempferol, hesperidin, apigenin, genistein) were test according to the theory of biopharmaceutics classification system (BCS), and their absorption mechanism. The solubility was investigated by the method in determination of solubility of "Chinese Pharmacopoeia 2010". To detect appearance permeability of compounds mentioned above, the appropriate concentrations were selected by the MTT method in cell transfer experiments in Caco-2 cell model, which established by in vitro cell culture method. Therefore, these compounds were classified with BCS according to solubility and permeability. In addition, to explore absorption mechanisms, the experiments in three different concentrations of compounds in high, medium and low in bidirectional transformation methods in Caco-2 cell model contacted. The study indicated that all of kaempferol, hesperidin, apigenin, genistein have the characteristics in low solubility and high permeability, which belong to BCSⅡ, and the absorption mechanism of kaempferol was active transportation. Whereas, hesperidin, apigenin, genistein were passive transportation. In this study, it carried out initial explorations on establishment of determination for solubility and permeability in flavonoids, and provided theoretical reference for further research on BCS in traditional Chinese medicine.

Over-expression of Sox4 and β-catenin is associated with a less favorable prognosis of osteosarcoma / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to examine the association of the expression of Sox4 and β-catenin with the prognosis of osteosarcoma. A total of 108 cases of conventional osteosarcoma were involved in this study and 28 cases of osteochondroma served as controls. The expression of Sox4 and β-catenin was detected by using immunohistochemical staining and Western blotting. The results showed that Sox4 and β-catenin were over-expressed in 67 (62.03%) and 62 (57.41%) of 108 osteosarcoma cases, while in only 3 (10.71%) and 5 (17.86%) of 28 controls, respectively (P<0.05 for all). The expression of Sox4 and β-catenin was associated with the distant metastasis, pathological grade and Enneking stage of patients with osteosarcoma (P<0.05 for all). The mean overall survival time and the 5-year-survival rate in osteosarcoma patients with Sox4 and β-catenin over-expressed were significantly reduced as compared with those in Sox4 and β-catenin low-expression group (P<0.05 for all). Cox multifactor regression analysis revealed that the distant metastasis, Enneking stage, and the expression of Sox4 and β-catenin were independent risk factors of patients with osteosarcoma (P<0.05 for all). The findings indicated that overexpression of Sox4 and β-catenin is associated with a poor prognosis of osteosarcoma.

Study of effects of micheliolide on ovarian cancer cell lines and its mechanism / 中华妇产科杂志

Objective To study the roles of micheliolide on ovarian cancer cells. Methods Firstly, human ovarian cancer cell lines HeyA8, SKOV3 and A2780/DDP were treated with different concentration of micheliolide (0.25, 0.5, 1, 2.5, 5, 10, 20, 50 μmol/L) for 72 hours, then methyl thiazolyl tetrazolium (MTT) assay was used wo detect the growth of the human ovarian cancer cell lines and the stongest inhibited cell line were selected for the following test. Secondly, after HeyA8 cell line was treated with different concentration (5, 10, 20μmol/L) of micheliolide for 24 hours, the HeyA8 cell apoptosis was measured byflow cytometry. Thirdly, the expression of RelA mRNA in HeyA8 cell was detected through real-time PCR, the expressions of nuclear factor κB(NF-κB)signal pathway related protein RelA and the activited cysteinyl aspartate specific proteinase (caspase-9) were detected by western blot analysis. Results (1) The growth of HeyA8, SKOV3 and A2780/DDP cells were all significantly inhibited after being treated with different concentration of micheliolide for 72 hours and the roles of inhibition were all concentration dependant (P<0.05). The half maximal inhibitory concentration (IC50) of HeyA8, SKOV3 and A2780/DDP were (9.8±2.2), (12.0±2.1) and (12.8±1.8)μmol/L, respectively. We chose HeyA8 cell to do the following expreriments because of its best inhibited effect. (2) After HeyA8 cell was treated with micheliolide of different concentrations, as the concentration increased (20 and 0μmol/L, for example), the apoptosis rate of HeyA8 cell raised from (7.2±1.0)%to (17.4±1.1)%, the percentage of survived cells reduce from (92.8 ± 1.3)% to (82.6 ± 1.4)%,and the relative mRNA level of RelA decreased from 1.00 ± 0.13 to 0.18 ± 0.00 (P<0.01); furthermore, the expression of RelA protein was weaken and the activited caspase-9 protein expression was increased gradually. Conclusions Micheliolide plays a significantly inhibited role in HeyA8, SKOV3 and A2780/DDP cells. The inhibited role of micheliolide inovarian cancer cells might through inhibiting nuclear factor-kappa B (NF-кB) signaling pathway, and inducing the expression of activited caspase-9 protein to promoting apoptosis of HeyA8 cell.