Objective To determine the anatomical and visual outcome of indocyanine-green (ICG)-assisted internal limiting membrane (ILM) peeling for idiopathic macular holes. Methods Thirty-one eyes of 31 patients with 3- (14 eyes, 45.2%) and 4-staged (17 eyes, 54.8%) primary idiopathic macular holes were analyzed. All the patients underwent the subtotal pars plana vitrectomy with removal of the posterior vitreous. ICG solution with the concentration of 1.25 mg/ml was injected into vitreous cavity. The ILM was stained and removed in a circular fashion of 2 to 3 disc-diameter from the edge of the hole. At the end of the surgery, 14% C 3F 8 mixed gas was used and the patients were required to maintain a prostrate posture for two weeks postoperatively. The mean follow-up duration was 9.1 months. Results The preoperative median visual acuity was 20/200. In the final follow-up, 28 eyes (90.3%) had anatomical restoration of the macular holes, 21 eyes had improvement of two lines or more of visual acuity. There was no direct complication or toxicity related to ICG-assisted ILM peeling except one patient with retinal detachment caused by peripheral retinal hole. Conclusion ICG-assisted retinal ILM removal appears beneficial and safe for primary idiopathic 3 and 4-staged macular holes.

Three active compounds were isolated from the marine bryozoan Bugula neritina living in the South China Sea by bioassay-guiding isolation method with a combination of extraction with suitable solvent and multiple column chromatography(Sephadex LH-20, ODS and preparative HPLC). Their structures were assigned as known bryostatin 4, bryostatin 5 and bryostatin 6 by intensive analysis of the data of high resolution 2DNMR(600 MHz,DQF-COSY,TOCSY,HMQC and ROESY). All these compounds were obtained from this bryozoan in the South China Sea for the first time and showed significant antineoplastic activities in vitro.

Glioma is the most common form of brain cancer. Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to its infiltrative nature. It has important significance to improve the treatment of glioma through in-depth understanding the intracerebral metabolic characteristics and pharmacokinetics of chemotherapeutics. Brain microdialysis (B-MD), an effective method to monitor central nervous system anticancer drug disposition, conditions of drugs through the blood-brain barrier, basic pathophysiologic metabolism, bioactive compounds and the changes of neurotransmitter in brain, provides the unique opportunity to allow the simultaneous determination of unbound concentrations of drugs in several tissues, and directly measure gliomas biochemistry continuously. B-MD has been able to monitor the change of brain drugs, metabolites and neurotransmitters, dynamic analysis of the drug concentration and pharmacological effect after administration, pharmacodynamic interaction between drugs, receptor mechanism of drug transport, as well as feedback information of internal environment. B-MD is expected to provide reference for clinical individual chemotherapy of glioma, but also provide powerful tools for the evaluation of new anticancer drugs in vivo. In this review, a comprehensive overview of B-MD for studies on glioma is elucidated with special emphasis on its application to neurochemistry and pharmacokinetic studies.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Blood-Brain Barrier ; Brain Neoplasms ; metabolism ; Glioma ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Metabolomics ; methods ; Microdialysis ; methods ; Neurotransmitter Agents ; pharmacokinetics ; Pharmaceutical Preparations ; metabolism ; Positron-Emission Tomography

Eight active compounds were isolated from Bugula neritina Linnaeus collected off Dapen Bay in Guandong province, guided by P 388 bioassay system by a combination of successive chromatographies and preparative HPLC. By intensive analysis of the data of high resolution 2D NMR spectrum and ESI MS, their structures were elucidated as known bryostatins--bryostatin 4, 5, 6, 8, 10, 11, 16 and 18, among which bryostatin 8 and 16 were for the first time obtained from this animal in South China Sea and they showed significant antineoplastic activities in vitro.

The epidemic of COVID-19 has brought great challenges to the global public health prevention and control system combined with clinical diagnosis and treatment system, and it makes the development of effective antiviral drugs an important task in current pharmaceutical research. Traditional Chinese medicine (TCM) has played an important role in the prevention and control of COVID-19. Due to its numerous chemical components and various structural types, TCM becomes a natural library for searching for lead compounds against SARS-CoV-2. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed for S protein receptor binding domain (SRBD) and angiotensin converting enzyme 2 (ACE2) which are two key proteins in the process of SARS-CoV-2 invading cells according to characteristics of synergistic effects of multiple components and comprehensive regulation of multiple targets of TCM. The SPR biosensor was applied to screen and identify active components from six TCMs, and daidzin from Puerariae Lobatae Radix was identified to bind with SRBD and ACE2. The affinity constant (K_D) of daidzin and ACE2 was 5.18 μmol·L^-1 through the SPR affinity assay. Competitive ELISA assay showed that daidzin could inhibit the binding of SRBD and ACE2, and the inhibition rate of daidzin (20 μmol·L^-1) was 38.6%. Molecular docking experiments further confirmed that daidzin had the best binding near the binding region of SRBD-ACE2 complex. This study shows that the dual-target SPR screening system is accurate and efficient, and is particularly suitable for screening of complex drug systems and effective substances study of TCM. It provides a material basis for exploring the mechanism of TCM active constituents against SARS-CoV-2, and provides a source of lead compounds for the development of anti-SARS-CoV-2 drugs.

OBJECTIVETo investigate the effects of anti-infection treatment on the expressions of antigen-presenting-related membrane-surface molecules HLA-DR and CD86 in dendritic cells (DCs) in rabbit buccal VX2 squamous cell carcinoma tissue complicated with local inflammation.

METHODSRabbit buccal VX2 squamous cell carcinoma with local inflammation models that were established by inflammation was induced by inoculation VX2 tumor, mechanical trauma, and drinking of milk with high sugar viscosity. The animals were divided into four groups. Group A (n=12): rabbit buccal VX2 squamous cell carcinoma with local inflammation, procaine penicillin was intramuscularly given, and tinidazole tablets were given by gavage for three consecutive days. Group B (n = 12): rabbit buccal VX2 squamous cell carcinoma with local inflammation, normal saline was intramuscularly given, and aspirin were given by gavage for three consecutive days. Group C (n = 12): rabbit buccal VX2 squamous cell carcinoma with local inflammation, normal saline was given intramuscularly and by gavage for three consecutive days. Group D (n = 10): rabbit buccal VX2 squamous cell carcinoma, normal saline was given intramuscularly and by gavage for three consecutive days. All the rabbits were sacrificed for collection of tumor specimens, and the expression levels of membrane-surface HLA-DR and CD86 in DCs of tumor specimens were detected viaflow cytometry.

RESULTSThe positive expression rate of HLA-DR and the double positive expression rate of HLA-DR and CD86 were group A > group D > group B > group C. The positive expression rate of CD86 were group A > group D > group B and group C (P < 0.05).

CONCLUSIONAnti-infection treatment significantly increased the expressions of HLA-DR and CD86 in DCs of rabbit buccal VX2 squamous cell carcinoma tissue complicated with local inflammation.

Animals ; Carcinoma, Squamous Cell ; immunology ; Dendritic Cells ; HLA-DR Antigens ; metabolism ; Inflammation ; Rabbits

OBJECTIVETo explore the effects of aspirin and inflammation on the maturation and function of dendritic cells (DC) on the supernatant of VX-2 squamous cell carcinoma.

METHODSThe rabbit buccal VX-2 squamous cell carcinoma models with inflammation were established by tumor particle implantation, mechanical trauma, and high sugar diet. The rabbits were divided into three groups. For the experimental group (rabbit buccal VX-2 squamous cell carcinoma with local inflammation), aspirin were given by gavage for three consecutive days. For the control group (rabbit buccal VX-2 squamous cell carcinoma with local inflammation), normal saline was given by gavage for three consecutive days. For the blank group (tumor without inflammation), normal saline was given by gavage for three consecutive days. Each tumor specimens were collected in three days and made into tissue homogenate. The supernatant was collected after centrifugation. Normal rabbit peripheral blood mononuclear cells were separated and co-cultured with different states of supernatant. The expression of DC surface markers CD83, CD86, and human leukocyte antigen-DR (HLA-DR) were detected by flow cytometry. The state of function of DC was tested by mixed lymphocyte reaction.

RESULTSThe positive rate of CD83, CD86, and HLA-DR of the experimental and control groups were both lower than that of the blank group (P<0.05). In addition, the ability to stimulate T cell proliferation of the experimental and control groups were weaker than that of the blank group (P<0.05). No significant difference was observed between the experi- and HLADR of DC. The short-term administration of aspirin is not conducive to the phenoty and function of DC in a rabbit mental and control groups (P>0.05).

CONCLUSIONInflammation may inhibit the function and expression of CD83, CD86, buccal VX-2 squamous cell carcinoma inflammatory environment

Animals ; Aspirin ; pharmacology ; Carcinoma, Squamous Cell ; Coculture Techniques ; Dendritic Cells ; drug effects ; Flow Cytometry ; Humans ; Inflammation ; Leukocytes, Mononuclear ; Organothiophosphorus Compounds ; Rabbits

Objective To investigate the preventive effect of Indomethacin for post-ERCP pancreatitis and hyperamylasemia.Methods A total of 600 patients,who were undergoing ERCP,were randomly divided into 3 groups to receive anal Indomethacin (n=200),intravenous octreotide (n=200) or no special medication (n=200) before ERCP.The level of serum amylase before and 24h after ERCP were measured,and the rate of acute pancreatitis and hyperamylasemia after ERCP were assessed.Results Serum amylase levels before ERCP of all groups were normal.The mean serum amylase level of Indomethacin group (101.3±77.7 U/L) after ERCP was significantly lower than those of octreotide group ( 176.6±138.3 U/L,P =0.040 ]and control group (227.2±264.9 U/L,P=0.048),while there was no difference between octreotide group and control group ( P＞0.05 ).The incidence of post-ERCP pancreatitis in Indomethacin group (2.5％) was significantly lower than that of control group (9.5％,P=0.003),while there was no difference between octreotide group (4.5％) and control group ( P=0.05 ).The incidence of hyperamylasemia after ERCP in Indomethacin group (5.5％) was significantly lower than that of control group ( 13.5％,P=0.006 ),while there was no difference between octreotide group (10.0％) and control group ( P＞0.05 ).Conctusion Anal administration of Indomethacin before ERCP can effectively reduce the incidence of acute pancreatitis and hyperamylasemia after ERCP.

Objective To set up a new diagnostic platform based on microarray exon-capture and next-generation sequencing for detecting small mutations in dystrophin gene.The sensitivity and specificity of the method were assessed in clinical settings and the distribution of small mutations in Chinese Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) patients were also analyzed.Methods Forty-one DMD/BMD patients diagnosed by the clinical criteria without large deletion or duplication (≥ 1exon) were recruited from Peking Union Medical College Hospital consecutively.Genomic DNA was extracted from blood samples.The libraries were prepared.Then exon and intron-exon flanking sequences of DMD gene were captured by custom microarray.Targeted next-generation sequencing and Sanger Sequencing were conducted.The patients who were not detected any disease-causing mutation were performed muscle biopsy.Results Thirty-eight subjects were detected small mutations in DMD gene.All single nucleotide variants (SNVs) and insertion & deletions (INDELs) were validated by Sanger sequencing.Twenty-one novel mutations were reported.The distribution of SNVs and INDELs was similar to other international DMD databases.Upon immunohistochemistry staining of dystrophin protein,1 of 3 mutation-undetected patients was diagnosed as DMD,2 of them were excluded.The specificity of the method was 100％,while the sensitivity was 97.4％.Conclusions Our microarray-captured next-generation sequencing assay could detect SNVs and INDELs with high sensitivity and specificity.Its advantages are economic,time-saving and stable.The platform is suitable for clinical gene diagnosis.

Objective To investigate the efficacy of concomitant precise hemihepateetomy for the treatment of hilar cholangiocarcinoma.Methods The clinical data of 38 patients with hilar cholangiocarcinoma who received concomitant precise hemihepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2009 to October 2012 were retrospectively analyzed.All patients were examined by B ultrasonography,computed tomography (CT),magnetic resonance cholangiopancreatography (MRCP) and CT angiography (CTA)preoperatively.The hepatic function was tested before operation.Of the 7 patients with obstructive jaundice,5 received percutaneous transhepatic cholangial drainage,and 2 received endoscopic nosalbiliary drainage.Surgical procedures were determined according to the results of imaging examination.The resection of hilar cholangiocarcinoma,postoperative histopathological examination,pre-and postoperative hepatic function and prognostic indicators were analyzed.The count data and measurement data were analyzed using the chi-square test and t test,respectively; the survival curve was drawn by Kaplan-Meier method,and the survival rate was analyzed using the Log-rank test.COX proportion hazards model was used for multivariate analysis.Results The positive rates of B ultrasonography,CT and MRCP were 65.8％ (25/38),71.1％ (27/38) and 89.5％ (34/38),respectively.The results of 5 patients who received CTA were positive.Concomitant left hemihepatectomy was performed on 28 patients,concomitant right hemihepatectomy on 10 patients; concomitant caudate lobectomy on 22 patients,concomitant resection and reconstruction of portal vein on 4 patients (including 1 patient who received left hepatic vein repair),concomitant hepatic artery resection on 12 patients (including 3 patients who received hepatic artery reconstruction).Of the 38 patients,R0 resection was performed on 32 patients,R1 resection on 4 patients,R2 resection on 2 patients.Hepatic function indicators including total bilirubin,direct bilirubin,alkaline phosphatase,gamma-glutamyl-transferase,alanine aminotransferase and aspartate aminotransferase were significantly decreased after operation (t =7.799,8.445,5.697,6.633,4.469,4.140,P ＜ 0.05).Two patients died perioperatively,with the mortality rate of 5.3％ (2/38).The main postoperative complications included bile leakage and hepatic function insufficiency,with the incidences of 28.9％ (11/38) and 21.1％ (8/38),respectively.Postoperative histopathological findings included 31 patients with invasive adenocarcinoma,5 patients with nodular adenocarcinoma,1 patient with mucinous adenocarcinoma and 1 patient with adenosquamous carcinoma.The overall 1-,2-,3-year survival rates were 66％,37％ and 21％,and the median survival time was 22.0 months.There were significant differences in the survival rates between patients who received R0 resection and those with R1/R2 resection,and between patients with N0 and N1/N2 stage (x2 =4.516,10.397,P ＜ 0.05).The results of multivariate analysis showed that positive margin and lymph node metastasis were prognostic indicators.Conclusions Concomitant precise hemihepatectomy has significantly improved the radical resection rate and the efficacy of treatment for hilar cholangiocarcinoma.Comprehensive preoperative imaging examination and hepatic function test are important for the assessment for resectability of hilar cholangiocarcinoma.Selective preoperative biliary drainage are key points to decrease postoperative morbidity and morality.