Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

ABSTRACT OBJECTIVE To investigate the children's medication information in β-lactam antibiotics's in children's hospitals in multiple regions, and to provide reference for further improving the drug information in the instructions of β lactam antibiotics. METHODS Collecting 847 drug instructions of β-lactam antibiotics in twenty children's hospitals in China, medication information labeling in drug instructions on children was investigated and analyzed. RESULTS After excluding duplicates, a total of 396 antibacterial drug inserts were obtained, involving 62 varieties, including 12 penicillins(59 copies), 27 cephalosporins(201 copies), etc. But there was two antibacterial drug for children only and up to 376 drugs for children and adults. In all drugs, there were 284 injections(71.72%) and 112 oral preparations(28.28%), among which the most suitable dosage forms for children were dry suspension(24.11%), granules(23.21%) and chewable tablets(4.46%). The annotation rates of children's indication, children's usage and dosage, children's drug guidance, pharmacokinetics in children, children's adverse reactions(396 categories) were respectively 27.78%, 93.69%, 64.65%, 39.14%, 20.96%, respectively. In oral dosage forms, the labeling rate of children's indications was 32.14%, the labeling rate of children's usage and dosage was 95.53%, the labeling rate of medication items for children was 58.93%, among them there were significant differences in the precautions and adverse reaction labeling rates between oral preparation and injections(P<0.05). There was not much difference in the labeling of pediatric medication information between domestic drugs and foreign-related drugs, but there was significant difference in the information labeling of precautions(P<0.05). There was no significant difference in the labeling rate of children's medication information among the seven regional children's hospitals. CONCLUSION There are few pediatric-specific β-lactam antibiotics, and the labeling information for pediatric use in their respective instructions is often incomplete and insufficient to provide meaningful guidance. Relevant departments should pay attention to the incomplete mark of drug use for children, improve the medication information of children in the instructions, and ensure the safety of pediatric drug use.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To investigate the CT signs of small intracranial aneurysm and the application value of multi-slice spiral CT angiography (MSCTA) before and after clipping surgery and in follow-up.Methods MSCTA imaging data of 81 patients with highly suspected small intracranial aneurysms from March 2013 to March 2015 were analyzed retrospectively.The confirmed patients underwent clipping surgery of small intracranial aneurysms.The imaging findings before and after clipping surgery were analyzed and compared with those by DSA and what observed during surgery.Results The relative accuracy,sensitivity and specificity of MSCTA over DSA and surgical diagnosis were 93.83％,93.75％ and 94.12％respectively,and MSCTA gained high relative consistency over DSA and surgical diagnosis (Kappa=0.825).The accuracy of MSCTA for diagnosing small intracranial aneurysm was not significantly different from those by DSA and surgical diagnosis.MSCT plain scan mainly showed subarachnoid or intracranial hemorrhage,and found 71 rhomboic or saccular aneurysms in 60 patients before operation.Totally 64 patients went through clipping surgery,60 ones had satisfactory results in the reexamination by MSCTA 2 weeks after surgery,and there were no abnormality found in 36 patients in 6 to 12-month follow-up.Conclusion MSCTA can provide abundant information for clipping surgery of small intracranial aneurysms,and can be used as the preferred imaging method for postoperative evaluation and follow-up.

Objective To evaluate the clinical efficacy of budesonide combined with ambroxol in the treatment of neonatal aspiration pneumonia.MethodsFrom January 2015 to January 2016 in our hospital 64 cases with neonatal aspiration pneumonia were randomly divided into two groups.The control group was treated with routine treatment, the study group used budesonide treatment, the treatment results were compared between the two groups.ResultsThe disappearance time of dyspnea, cyanosis, pulmonary rales and other symptoms and hospitalization time in study group were significantly shorter than those in the control group (P<0.01);the levels of interleukin(IL)-6, IL-8 and tumor necrosis factor alpha(TNF-α)in the study group after intervention were significantly lower than those in the control group (P<0.05) before treatment, PCT levels in two groups before treatment had no significant difference, three days, seven days and 14 days after the treatment PCT of the study group was significantly lower than the control group (P<0.05).ConclusionInhalation of budesonide and ambroxol in the treatment of neonatal pneumonia, can significantly improve the therapeutic effect, reduce the levels of inflammatory factors in children,can help the recovery of children.

Objective To investigate altered microstructural integrity in acute carbon monoxide(CO)intoxication by diffusion tensor imaging (DTI).Methods A total of 25 CO intoxication patients (5.0±1.44 post-intoxication)and 37 healthy volunteers matched with age, sex and educational level were involved and underwent DTI.The fractional anisotropy (FA)and apparent diffusion confficient (ADC) of total 26 regions of bilateral cerebellum,substantia nigra,hippocampus,white matter of frontal lobe,head of caudate nucleus,pallidum,thalamus, anterior limb of internal capsule,posterior limb of internal capsule,white matter of occipital lobe,white matter of parietal lobe,and genu of corpus callosum,splenium of corpus callosum were measured.Compared the patients against control for FA and ADC by paired t-test.Results FA of patients with CO intoxication decreased in bilateral pallidum,anterior limb of internal capsule,substantia nigra,right cerebellum,left below frontal white matter,right frontal white matter and genu of corpus callosum (P <0.05).ADC decreased in right substantia nigra,and left pallidum (P <0.05).ADC increased in right frontal white matter and bilateral occipital lobe white matter (P<0.05).Conclusion There is loss of microstructural integrity in acute CO intoxication,perhaps representing the underlying mechanism of delayed encephalopathy after carbon monoxide poisoning.

Objective To investigate the effect and mechanism of liver cancer derived mesenchymal stem cell (LCMSC) on the invasion of liver cancer cells. Methods The expressions of interleukin (IL)-6, IL-8 and chemotactic factors CXCL1, CXCL5 and CXCL12 mRNA in the bone marrow derived mesenchymal stem cell (BMSC) and LCMSC were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of protein CXCL12 in the supernate of LCMSC was detected by enzyme-linked immunosorbent assy (ELISA) and Western blot. Different cells were co-cultured and divided into the HepG2+BMSC, HepG2+LCMSC and HepG2+LCMSC+siRNA-CXCL12 groups. The effect of CXCL12 on the invasion of liver cancer HepG2 cells were detected by Transwell migration assay. The experiment data were compared using one way analysis of variance and LSD-t test or t test. Results The expression of CXCL12 mRNA in LCMSC was 60.3±2.4, significantly higher than 13.8±1.8 in BMSC (t=15.68, P<0.05). The expression of protein CXCL12 in the supernate of LCMSC was (31.5±1.7) ng/L, significantly higher than (14.3±1.5) ng/L in BMSC (t=7.60, P<0.05). And the expression of protein CXCL12 was up-regulated. Transwell migration assay indicated that the quantity of membrane-invasion cells in the HepG2+LCMSC group was 110±12, significantly higher than 65±9 in the HepG2+BMSC group and 76±7 in the HepG2+LCMSC+siRNA-CXCL12 group (LSD-t=5.25, 4.86; P<0.05). Conclusion CXCL12 is highly expressed in LCMSC. LCMSC may enhance the invasion of HepG2 cells through up-regulating the expression of CXCL12. The invasion of liver cancer cells can be effectively weakend by silencing the CXCL12 gene with siRNA.

Objective:To investigate the change of liver function,viral load and CD4+T count in pediatric AIDS patients with HBV/HCV co-infection after HARRT therapy,and explore the effect of HBV/HCV co-infection on HAART.Methods:95 pediatric AIDS patients without HBV/HCV co-infection ( group A) ,9 pediatric AIDS patients with HBV co-infection ( group B) and 23 pediatric AIDS patients with HCV co-infection ( group C) who received HAART for 2 year were enrolled.Liver function,viral load and CD4+T count were detected before and after HAART.Results:After HAART for 2 years,26 patients (20.5%) were found with liver injury of grade 2 (1000.05 ) .Conclusion: Co-infection of HBV/HCV can aggravate the liver damage of HIV-1 infected children,but has no significant effect on HAART.

Animals ; Autoantibodies ; blood ; Cytokines ; biosynthesis ; Dose-Response Relationship, Drug ; Female ; Immunohistochemistry ; Rats ; Rats, Inbred Lew ; Selenium ; administration & dosage ; therapeutic use ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology ; Thyroid Gland ; drug effects ; immunology ; pathology ; Thyroiditis, Autoimmune ; drug therapy ; immunology ; Trace Elements ; administration & dosage ; therapeutic use

Objective To discuss the preschool children after hepatitis B vaccines injected,the variation trend of hepatitis B surface antibody (HBsAb)'s positive rate- Methods 4149 preschool children's HBsAb were examined ,by means of enzyme linked immunosorbent assay(ELISA). Results The HBsAb's positive rate among the age from 0～2,2.1～3.0,3.1～4.0,4. 1～5.0,5.0～6.0,for each age period,children's HBsAb positive rates was 64.65% ,68.64% ,71.55% ,74.21%,68.38% respectively. The statistical analysis showed that there was statistcal significance(x2=19.77, P