Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer / 中西医结合学报

OBJECTIVE@#Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems.@*METHODS@#A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system.@*RESULTS@#DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 °C than 37 °C. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors.@*CONCLUSION@#DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.

Application of 3g/L sodium hyaluronate eye drops combined with corneal bandage contact lens in the early stage after pterygium excision surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the application value of 3g/L sodium hyaluronate eye drops combined with corneal bandage contact lens in the early stage of pterygium excision surgery.<p>METHODS: In this double blind randomized controlled study, 90 eyes of 90 patients with unilateral primary nasal pterygium who underwent surgical treatment from March 2017 to March 2018 were sorted into three groups, named as group A, group B and group C. Group A was treated with +3g/L sodium hyaluronate eye dropsand corneal bandage contact lens; group B was treated with +1g/L sodium hyaluronate eye drops and corneal bandage contact lens; and group C with +3g/L sodium hyaluronate and patching. Ocular surface irritation symptom scores, corneal epithelial healing time and conjunctival graft edema subsidence time of the three groups were compared after treatment.<p>RESULTS: Ocular surface irritation symptom scores in group A were lower than those in group C at all observation time points postoperatively(all <i>P</i><0.001); the corneal epithelial healing time(2.08±0.78d)and conjunctival graft edema subsidence time(4.62±1.17d)in group A were significantly shorter than those in group C with corneal epithelial healing time(5.13±2.34d)and conjunctival graft edema subsidence time(6.42±1.51d)(<i>P</i>=0.001, <i>P</i>=0.002). The corneal epithelial healing time was significantly shorterin group A when compared with group B(<i>P</i>=0.018), but there were no significant differences in ocular surface irritation symptom scores and conjunctival graft edema subsidence time between the two groups.<p>CONCLUSION: The combination of 3g/L sodium hyaluronate and corneal bandage contact lens has synergistic effect when applicated in the early stage after pterygium excision surgery, it can effectively shorten the corneal epithelial healing time as well as relieve irritation symptoms.

The correlation between the carotid artery plaque and the change of aldosterone level related indexes during captopril challenge test / 中国应用生理学杂志

OBJECTIVE@#To investigate the correlation between the carotid artery plaque and the change of plasma aldosterone level related indexes during captopril challenge test.@*METHODS@#The patients with hypertension were enrolled as research objects and the captopril challenge test were carried out when they were hospitalized to screen the cause of hypertension. There were intact carotid artery duplex ultrasonography diagnostic data in them (83 cases). They were divided into the plaque group(57 cases) with carotid artery plaque and no plaque group( 26 cases) without carotid artery plaque according to the carotid artery duplex ultrasonography diagnostic data. The correlation between the carotid artery plaque and the changes of aldosterone concentration, renin activity and aldosterone to renin activity ratio(ARR) in two groups were analyzed.@*RESULTS@#The detection rate of carotid artery plaque was 68.67%. Compare with no plaque group, the patients in plaque group were elder and the level of apolipoprotein A1,(APOA1) was lower (all P＜0.05). The ARR difference value before and after captopril challenge test was lower ( P＜0.05).The aldosterone difference value and the renin activity difference value before and after captopril challenge test were higher in plaque group (all P＜0.05).The aldosterone difference value and the renin activity difference value were positive in plaque group and were negative in no plaque group. The difference value of the ARR was negative in plaque group and was positive in no plaque group. Logistic regression analysis showed that the age, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence after excluding gender difference and other factors.@*CONCLUSION@#The detection rate of carotid artery plaque was high among hospitalized patients with hypertension, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence.

Precision medicine and nanomedicine: Two essential and interdependent elements in precision therapy / 第二军医大学学报

Precision medicine has shown a new hope for cancer treatment because it can provide clear individual disease causes, precision therapeutic targets and accurate classification based on the genome sequencing, bioinformatics, and large database. However, the effective precision therapy should also include how to deliver and release drugs with controlled dosage at the precision therapeutic targets. A challenge in clinical anti-tumor precision therapy is how to achieve precision delivery and regulate the dosage of screened drugs, including how to overcome the biological barrier, how to safely deliver the drugs to nidus, how to enhance intratumoral accumulation of drugs, how to promote endocytosis of target cells, and how to accurately deliver drugs to intracellular therapeutic targets. Nanomedicine can effectively solve the problems as mentioned above. Through fine design and nanocarrier tailoring, nano-products will accurately and efficiently deliver the screened drug molecules to target organs, target tissues, target cells or intracellular target organelles, and precisely release the drug to a desirable dosage under the stimulation of lesions. The combination of precision medicine and nanomedicine can efficiently achieve precision therapy: from the tumor molecular classification, drug screening, drug precision delivery, controlled drug release to the treatment. Consequently, precision medicine mainly refers to accurate diagnosis and accurate screening of drug targets, which is the so called “advance troops and scouts” of precision treatment of cancer. Nanomedicine mainly focuss on the accurate delivery and controlled release of drugs to the therapeutic target, which can be called “accurate strategic bombing”. Both precision medicine and nanomedicine are essential and interdependent elements in precision therapy.

Study on efficacy and visual sensitivity of long-term masking therapy for children with ametropic amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the efficacy and visual sensitivity of occlusion therapy combined training for children with ametropic amblyopia.METHODS:Totally 85 children (85 eyes) with anisometropic amblyopia treated in our hospital from January 2013 to January 2015 were selected.All patients were given occlusion therapy combined training.Statistical analysis of clinical efficacy and visual sensitivity changes were taken,and the changes of visual acuity,AULCSF,S Frmax were analyzed.RESULTS:The visual acuity after therapy was significantly better than that before treatment (1.12±0.29 vs0.45±0.25,P＜0.01);AULCSF,Smax and Frmax all increased,the difference between the two groups was statistically significant (P＜ 0.05).The sensitivity of the same spatial frequency was significantly higher than that before treatment,the difference was statistically significant (P ＜ 0.05),and the contrast sensitivity decreased gradually with the increase of spatial frequency.There were statistical differences in the total effective rate of different refractive degrees after treatment (P=0.001).Mild group and moderate group had no significant difference on the total clinical efficiency difference (x2=3.091,P=0.079);between mild group and severe group total effective rate was significantly different (x2 =11.471,P =0.001);the moderate and severe groups total clinical efficiency were no significantly different (x2 =3.359,P=0.067).In addition,the total efficiency rate of wearing glasses under the age of 6 was significantly higher than that after 6 years old (95％ vs 77％),statistical difference between the two groups was significant (P＜0.05).CONCLUSION:Masking therapy combined with comprehensive training,in the treatment of children with ametropic amblyopia,and wearing a corrective spectacles,is desirable,especially for children under 7 years of age.

Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivo / 中国药理学与毒理学杂志

OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms. METHODS ULK1 expression was analyzed by The Cancer Genome Atlas (TCGA) analysis and tissue microarray (TMA) analysis. ULK1 agonist was designed by using in silico screening, as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities. The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis, as well as in vitro kinase assay and ADP-Glo kinase assay. The mechanisms of LYN-1604 induced cell death were investigated by fluores?cence microscope, western blotting, flow cytometry analysis, immunocytochemistry, as well as siRNA and GFP-mRFP-LC3 plasmid transfections. Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model. RESULTS We found that ULK1 was remarkably downregulated in breast cancer tissue samples, especially in triple negative breast cancer (TNBC). 32 candidate small molecules were synthesized, and we discovered a small molecule named LYN-1604 as the best candidate ULK1 agonist. Additionally, we identified that three amino acid residues (LYS50, LEU53 and TYR89) were key to the activation site of LYN-1604 and ULK1. Subsequently, we demonstrated that LYN-1604 could induce autophagy-associated cell death via ULK complex (ULK1-mATG13-FIP200-ATG101) in MDA-MB-231 cells. We also found that LYN-1604 induced cell death involved in ATF3, RAD21 and caspase 3, accompanied with autophagy and apoptosis. Moreover, we demonstrated that LYN-1604 had a good therapeutic potential on TNBC by targeting ULK1- modulated cell death in vivo. CONCLUSION We discovered a small molecule (LYN-1604) has therapeutic potential by targeting ULK1-modulated cell death associated with autophagy and apoptosis of TNBC in vitro and in vivo, which could be utilized as a new anti-TNBC drug candidate.

Triterpenoid saponins from Patrinia scabra / 中国天然药物

AIM@#To study the chemical constituents and bioactivity of the roots of Patrinia scabra Bunge.@*METHODS@#The chemical constituents were isolated using various chromatographic methods, and the structures were elucidated on the basis of spectral analysis and chemical methods. In addition, cytotoxic activities toward HepG2 cells were tested by the MTT method.@*RESULTS@#A new triterpenoid saponin, 3-O-(4'-isovaleryl)-O-β-D-xylose-12,30-dihydroxy-oleanane-28,13-lactone-22-O- β-D-glucoside (1), along with two known triterpenoid saponins, acanthopanax saponin CP3 (2) and foetoside C (3), were isolated.@*CONCLUSION@#The aglycone of compound 1 was a new skeleton derivative of oleanolic acid. Compound 2 showed strong cytotoxicity to HePG2 cells (IC50 1.49 μmol·L(-1)).

Mid-long-term curative effect analysis of complex acetabular fracture / 中国骨伤

<p><b>OBJECTIVE</b>To discuss clinical effects of complex acetabular fracture.</p><p><b>METHODS</b>From January 2005 to December 2010, totally 31 patients with complex acetabular fracture received surgery. There were 21 males and 10 females with an average age of 38.6 years old (ranged, 31 to 57). X-ray, CT, operation scheme and clinical efficiacy were retrospectively analyzed. American Academy of Orthopaedic Surgery standard was used to evaluate hip joint function.</p><p><b>RESULTS</b>All patients were followed up from 12 to 36 months with an average of 17.6 months. No complications and neurovascular injury occurred. One case received total hip replacement arthroplasty. There were 17 cases obtained anatomical reduction, 12 cases got satisfied reduction and 2 cases not satisfied. According to American Academy of Orthopaedic Surgery standard, 18 cases got excellent result, good in 9 cases, fair in 3 cases and poor in 1 case.</p><p><b>CONCLUSION</b>Complex acetabular fracture combine with lots of complications and easily had occurre postoperative complications. It can improve curative effect by accurate reduction and reliable fixation and maximize restoring function of hip joint.</p>

Clinicopathological features of non-familial colorectal cancer with high-frequency microsatellite instability / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To explore the clinicopathological features of non-familial colorectal cancer with high-frequency microsatellite instability (MSI-H).</p><p><b>METHODS</b>One hundred and fifty patients with colorectal cancer who had no family history were enrolled in this study from June 2006 to June 2008. Five standard microsatellite loci including BAT25, BAT26, D2S123, D5S346, and D17S250 were amplified with immunofluorescent polymerase chain reaction. The patient information including age, sex, and tumor location was recorded. Pathological features including differentiation, mucinous differentiation, histological heterogeneity, and Crohn's-like reaction were observed under light microscope. The presence of tumor-infiltrating lymphocytes (TLs, CD4+ and CD8+) was detected by means of immunohistochemistry. A regression equation was obtained by stepwise logistic regression analysis to evaluate the relationship between MSI-H phenotype in colorectal cancer and pathological features.</p><p><b>RESULTS</b>MSI-H phenotype occurred in 13.33% of the 150 patients with non-familial colorectal cancer. Poor differentiation, histological heterogeneity, Crohn's-like reaction, and presence of TLs were found to be independent factors to identify MSI-H non-familial colorectal cancer. Logistic regression equation showed an overall sensitivity of 70.0%, specificity of 99.2%, and accuracy of 95.3% in identifying MSI-H non-familial colorectal cancer.</p><p><b>CONCLUSION</b>MSI-H non-familial colorectal cancer manifests specific pathological features, which may be relied upon for effective identification of that disease.</p>

Study on technology of extracting geniposidic acid from Eucommia ulmiodes and its application / 中国中药杂志

<p><b>OBJECTIVE</b>To study the optimum technology of extracting bioactive component named geniposidic acid in Eucommia Ulmiodes by orthogonal test.</p><p><b>METHOD</b>An orthogonal test table L16(4(5)) was used with the factors of extracting time, temperature, times, ethanol consistency and the ratio of solid to liquid. The content of geniposideic acid was determined by RP-HPLC.</p><p><b>RESULT</b>The optimum technology was: temperature 50 degrees C, time 1 h, once, consistency 80%, and the ratio of solid and liquid 1:12. Under the condition, the best material of Eucommia Ulmiodes for extracting geniposidic acid was chosen.</p><p><b>CONCLUSION</b>The technology can provide some theoretic advice for industry.</p>

Quantitative study on depth of ketamine anesthesia for preschoolers / 实用儿科临床杂志

Objective To compare and quantify the determinants in quantitative electroencephalogram(q-EEG) and heart rate variability power spectrum analysis(HRV-PSA) of ketamme(KTM) anesthesia for preschoolers. Methods Seventy four cases were selected and assigned into 3 groups named A(4-5 years), B(5-6 years), C(6-7 years), 22,28,24 cases in every group respectively. All cases were induced with KTM 5 mg /kg intramuscularly and changes of determinants were recorded continuously. If body movement happened, KTM would be injected with 1 mg/kg. Results On pre- anesthesia, BIS in group A was the least among 3 groups, while LF/HF and HRVI were the largest(P