The influence of the extent of lymph node metastasis on the prognosis for patients with intrahepatic cholangiocarcinoma

Purpose@#Reports showed that some of intrahepatic cholangiocarcinoma (ICC) patients with lymph node metastasis (LNM) may also gain survival benefit undergone resection. However, the effect of the extent of LNM on prognosis and surgical indication is barely discussed. @*Methods@#From September 1994 to November 2018, primary ICC patients undergone initial curable surgery were enrolled. Based on the extent of LNM, we divided these patients into 4 groups, including patients with no LNM (group N0), LNM to hepatoduodenal ligament or common hepatic artery (region A, group A), LNM to gastrohepatic lymph nodes for left liver ICC and periduodenal and peripancreatic lymph node for right liver ICC (region B, group B), or LNM beyond these regions (region C, group C). Multivariable Cox regression analysis was performed to identify the prognostic factors for recurrencefree survival (RFS) and overall survival (OS) in all groups. @*Results@#A total of 133 patients were enrolled. There were 56, 21, 17, and 39 patients in groups N0, A, B, and C, respectively. There was significant difference between groups N0 and C in RFS (P < 0.001) and OS (P = 0.002). When we compared group N0 + A + B with group C, we also found that RFS (P < 0.001) and OS (P = 0.007) were significantly different. In multivariable analysis, the extent of LNM was an independent risk factor for RFS (P < 0.050). @*Conclusion@#ICC patients with the LNM to regions A and B could still achieve good prognosis with resection. Surgery should be carefully considered when LNM to region C.

A Nested Case-Control Study to Explore the Association between Immunoglobulin G N-glycans and Ischemic Stroke / 生物医学与环境科学（英文）

OBJECTIVE@#This study prospectively investigates the association between immunoglobulin G (IgG) N-glycan traits and ischemic stroke (IS) risk.@*METHODS@#A nested case-control study was conducted in the China suboptimal health cohort study, which recruited 4,313 individuals in 2013-2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. IgG N-glycans in baseline plasma samples were analyzed.@*RESULTS@#A total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks (GPs) were separated from IgG N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference, obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men (FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio ( OR) = 0.92, 95% confidence interval ( CI): 0.87-0.97; G1 n: OR = 0.74, 95% CI: 0.63-0.87; G0 n: OR = 1.12, 95% CI: 1.03-1.22). However, these associations were not found among women.@*CONCLUSION@#This study validated that altered IgG N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations.

Therapeutic effect and mechanism of Xiaoyao Kangai Jieyu Recipe on mice with breast cancer related depression through regulating COX pathway / 中国中药杂志

This study aimed to investigate the intervention effect and mechanism of Xiaoyao Kangai Jieyu Recipe(XKJR) on hip-pocampal microglia and neuronal damage in mice with breast cancer related depression. The mouse model of breast cancer related depression was established by inoculation of 4T1 breast cancer cells in axilla and subcutaneous injection of corticosterone(30 mg·kg~(-1)). The successfully modeled mice were randomly divided into a model group, a positive drug group(capecitabine 60 mg·kg~(-1)+fluoxetine 19.5 mg·kg~(-1)), and XKJR group(19.5 mg·kg~(-1) crude drug), with 6 in each group. Another 6 normal mice were taken as a normal group. The administration groups were given corresponding drugs by gavage, while the normal and model groups were given an equal volume of distilled water, once a day for 21 consecutive days. The depressive behavior of mice was assessed by glucose consumption test, open field test and novelty-suppressed feeding test. Hematoxylin and eosin(HE) staining and tumor suppression rate were used to evaluate the changes of axillary tumors. The mRNA expressions and the relative protein expressions of interleukin-1β(IL-1β), interleukin-18(IL-18), cyclooxyganese-2(COX-2) and glutamyl-prolyl-tRNA synthetase(EPRs) in the hippocampus of mice were determined by quantitative real-time polymerase chain reaction(qRT-PCR) and immunohistochemistry, respectively. Immunofluorescence was performed to detect the mean fluorescence intensity of CD11b, a marker of hippocampal microglia activation. Nissler staining and transmission electron microscopy were employed to observe the morphological changes and the ultramorphological changes of hippocampal neurons, respectively. The experimental results indicated that compared with the normal group, the model group had reduced glucose consumption and lowered number of total activities in open field test(P<0.05, P<0.01), prolonged first feeding latency in no-velty-suppressed feeding test(P<0.01), and significant depression-like behavior; the contents of IL-1β, IL-18, COX-2, and EPRs in hippocampus were increased(P<0.05, P<0.01), with hippocampal microglia activation and obvious neuronal damage. Compared with the model group, the positive drug group and the XKJR group presented an improvement in depressive behaviors, a decrease in the contents of IL-1β, IL-18, COX-2 and EPRs in hippocampus, and an alleviation in the activation of hippocampal microglia and neuronal damage; the tumor suppression rates of positive drug and XKJR were 40.32% and 48.83%, respectively, suggesting a lower tumor growth rate than that of the model group. In summary, XKJR may improve hippocampal microglia activation and neuronal damage in mice with breast cancer related depression through activating COX signaling pathway.

Effect of auricular point sticking therapy on perioperative pain in patients with partial lung resection / 中国针灸

OBJECTIVE@#To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection.@*METHODS@#A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TF@*RESULTS@#In 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately (@*CONCLUSION@#Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of β-endorphin.

Current Research Status of Aptamer-mediated Liposome Targeted Delivery of Antitumor Drugs / 中国实验方剂学杂志

Tumor has become the second most serious disease that threatens human health and life. Treating with chemical drugs (referred to as chemotherapy) is the most basic treatment, but most chemotherapeutic drugs cause damage to normal tissues. It is a difficult problem in the field of biomedical research that how to deliver anti-tumor drugs more efficiently, increase the concentration of drugs in tumor tissues, enhance the anti-tumor effect, and decrease the drug distribution in normal tissues to weaken the damage to normal tissues. In order to achieve the goals of accurate delivery of anti-tumor drugs and synergism and attenuation, the researchers used systematic evolution of ligands by exponential enrichment technology (SELEX technology) to screen aptamers that can specifically target tumor markers or tumor cells, and designed the novel liposome targeting drug delivery system with aptamers as targeting molecules (ligands). This paper briefly introduced nucleic acid aptamer technology and common tumor markers, and reviewed the research advances on the antitumor effect of aptamer-liposome drug delivery system. It will provide references for the selection of appropriate tumor markers as targets and the application of aptamer technology in the research and development of high-efficiency and low-toxicity liposome targeting agents of anti-tumor traditional Chinese medicine. Meanwhile, it is of great significance for promoting the application of aptamer technology in targeted drug delivery systems.

Effect of grain-moxibustion on neutrophil to lymphocyte ratio and quality of life in patients with advanced gastric cancer / 中国针灸

OBJECTIVE@#To observe the effect of grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) on neutrophil to lymphocyte ratio (NLR) and quality of life (QOL) in patients with advanced gastric cancer.@*METHODS@#Sixty patients with advanced gastric cancer were randomly divided into an observation group and a control group, 30 cases in each one. In the control group, conventional chemotherapy regimen combined with symptomatic treatment，such as antiemetic, acid-suppressive, liver-protecting drugs. On the basis of the treatment in the control group, grain-moxibustion was applied at Zusanli (ST 36) and Weishu (BL 21) in the observation group, 9 cones for each acupoint, once a day for a total of 90 days. The levels of NLR were observed before and after treatment, and the clinical efficacy and quality of life were evaluated in the two groups.@*RESULTS@#After treatment, the value of NLR in the observation group was significantly lower than before treatment (0.05), and the descend range of observation group was larger than the control group (0.05). After treatment, the QOL in the observation group was improved in diarrhea, loss of appetite, fatigue, nausea and vomiting, general health states (0.05), and the observation group was superior to the control group in fatigue, sleep disorder, loss of appetite, diarrhea and general health states after treatment (<0.05).@*CONCLUSION@#Grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) can decrease NLR and improve QOL of patients with advanced gastric cancer.

Effect of TSP-1 gene on angiogenesis of osteosarcoma and its mechanism / 实用肿瘤学杂志

Objective The aim of this study was to investigate the effect of TSP-1 gene on angiogenesis in human osteosar-coma and its mechanism of action. Methods MG-63 cells were transfected with constructing pBPLV-shRNA-TSP-1 vector and pBPLV-TSP-1 expression vector. Cell viability was measured by CCK8,and its invasive ability was measured by Transwell assay. The expression of CD36 in intracells was detected by immunofluorescence. The expression levels of TSP-1,CD36,p38MAPK,VEGF, VEGFR-1,EGF and PDGF were detected in MG-63 cells by qRT-PCR and Western blot. Results The cell viability and inva-sion ability were significantly increased after transfected pBPLV-TSP-1 vector compared with the empty vector group(P<0. 05), and significantly decreased after transfected pBPLV-shRNA-TSP-1 vector( P<0. 05). The expression of TSP-1,EGF,P38, PDGF,VEGF and VEGFR -1 at mRNA and protein levels was significantly increased after transfection pBPLV -TSP -1 ( P <0. 05),and significantly decreased after transfection pBPLV-shRNA-TSP-1 vector(P<0. 05). Conclusion TSP-1 gene can promote the proliferation and invasion of MG-63 cells,and promote the formation of human osteosarcoma,indicating its mechanism related to the increase of growth factors EGF,VEGF,PDGF and activation of P38-MAPK pathway.

Research Progress in Co-Delivery of Anti-multidrug Resistant Small RNA and Anti-tumor Drugs with Nanocarriers / 中国药学杂志

The efficacy of antineoplastic drugs in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. The formation mechanism of multidrug resistance is very complex. Conventional drugs or gene therapy usually only aim at a specific drug target, so it is difficult to effectively control the complex signaling pathways of drug-resistant cells. The co-delivery of small RNA (siRNA ormiRNA) and anti-tumor drugs with nanocarriers can maximize the synergistic effect, and reverse the multidrug resistance of tumor cells by silencing some related proteins. This review summarizes the mechanisms and advantages of the combination therapies involving RNA and antineoplastic drugs, in vitro and in vivo evaluation, as well as the recent advances in the co-delivery nanocarriers for these agents.

Preparation process of galactosylated liposome of modified cantharidin / 中草药

Objective To optimize the formulation ratio and preparation process of galactosylated cantharidin liposome (Lac-CTD- lips) and establish its methodology for content determination. Methods The method of determination of GC-MS cantharidin content was established by film dispersion method. The entrapment efficiency of cantharidin was evaluated as an index. The preparation process of Lac-CTD-lips was optimized by single factor and orthogonal experiments. Its surface characteristics, encapsulation efficiency, particle size, and Zeta potential were also investigated. Results The best prescription was as follow: cantharidin: hydrogenated soya lecithin:cholesterol at 1:20:5, 10% galactoside, film-forming at 50 ℃, film cleaning with 30 mL of PBS solution of pH 6.0, and hydartion at 40 ℃ for 1.5 h. The resulting liposomes exhibited a pale blue opalescent appearance, a spherical particle morphology, and a more rounded surface with no adhesion. The average particle size was (123.9 ± 4.8) nm (n = 3), the particle size distribution was single-peak, the zeta potential was (-0.36 ± 0.81) mV (n = 3), and the encapsulation efficiency was over 75%. Conclusion GC-MS is suitable for the determination and analysis of cantharidin content. The optimal preparation technology from orthogonal experiment is stable and reliable. The obtained liposomes have higher encapsulation efficiency, small particle size, and good appearance.

The Prognostic Value of CD8⁺ and CD45RO⁺ T Cells Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation

BACKGROUND: Postoperative cholangitis is a common but severe complication after Kasai portoenterostomy for biliary atresia (BA). This study aimed to identify its prognostic factors. METHODS: Two sets of liver paraffin-embedded tissue samples were collected from BA patients who received Kasai portoenterostomy (n = 25 and n = 31, respectively). Patients were divided into non-cholangitis and cholangitis groups. The infiltration of CD4+, CD8+, CD45RO+, CD68+ cells and expression of Beclin1 were quantitatively evaluated in immunohistochemical analysis. RESULTS: Cholangitis group had a significantly lower CD8+ T cell infiltration but a higher CD45RO+ cell infiltration, and a lower Beclin1 level than non-cholangitis group (all P < 0.01). Multivariate logistic regression analysis indicated that infiltration of CD8+ cells (odds ratio [OR], 0.112; 95% confidence interval [CI], 0.022–0.577) and CD45RO+ cells (OR, 3.88; 95% CI, 1.37–11.03), and Beclin1 level (OR, 0.088; 95% CI, 0.018–0.452) were independent influence factors for early postoperative cholangitis. Receiver operating characteristic (ROC) analysis showed that area under ROC curve (AUROC) values for CD8+ cells, CD45RO+ cells and Beclin1 were 0.857, 0.738 and 0.900, respectively. CONCLUSION: Our findings demonstrated the CD8+ cells, CD45RO+ cells and Beclin1 level possessed the prognostic value for early postoperative cholangitis following Kasai operation, which may be helpful to develop new prevention and treatment strategies for postoperative cholangitis.

Association between IgG N-glycans and Nonalcoholic Fatty Liver Disease in Han Chinese / 生物医学与环境科学（英文）

Nonalcoholic fatty liver disease (NAFLD) is a major public health issue worldwide. Immunoglobulin G (IgG) N-glycans are associated with risk factors for NAFLD, such as obesity and diabetes. A cross-sectional study involving 500 Han Chinese adults recruited from a community in Beijing was carried out to explore the association between IgG N-glycans and NAFLD. IgG N-glycosylation was significantly associated with NAFLD, with the disease showing a negative correlation with galactosylation (GP14, GP14n, and G2n), positive correlation with fucosylation (FBG2n/G2n), and positive correlation with bisecting N-acetylglucosamine (GlcNAc) [FBG2n/FG2n and FBG2n/(FG2n+FBG2n)], after controlling age, gender, and prevalence of obesity, type 2 diabetes mellitus, hypertension, and hyperlipidemia. In other words, the present study showed a possible association between NAFLD and the loss of galactose and elevations of fucose and bisecting GlcNAc. Aberrant IgG glycosylation might therefore be a potential biomarker for the primary or secondary prevention of NAFLD.

Clinical analysis on 13 cases of Kaposiform hemangioendothelioma / 中华实用儿科临床杂志

Objective To explore the diagnosis and treatment of Kaposiform hemangioendothelioma (KHE),deepen the understanding of KHE and Kasabach-Merritt phenomenon (KMP),and discuss the optimal treatment for KHE.Methods From January 2008 to August 2016,13 cases of KHE were confirmed by surgery or biopsy pathology and admitted to the First Affiliated Hospital of Sun Yat-Sen University,and the clinical diagnosis and treatment were analyzed retrospectively.Results There were 13 patients(7 males and 6 females) with a median age of 1.0 years(0.2-10.0 years),and 84.6%(11/13 cases) were infants and young children,76.9% (10/13 cases) involved with deep tissue,23.1% (3/13 cases) were associated with KMP and they were younger than 1 year old,and 15.4% (2/13 cases) coexisted with hemangioma or lymphangioma.The location,extent and infiltration depth of the lesion were observed by imaging examinations and histopathology showed nodule shaped spindle tumor cells.Radical resection was considered if possible.Dose of Vincristine (0.5 mg/m2 weekly) and Propranolol [1 mg/(kg·d)] were administered.The prognosis was different in thirteen cases undergoing different treatments.After 3 months to 9 years follow-up,41.7% (5/12 cases) survived after tumor treatment.Conclusions KHE happens mostly in infants and young children,with varying clinical manifestations and a high recurrence rate.The diagnosis of KHE is based on histological examination,computed tomography and magnetic resonance imaging while it still need explicit pathological diagnosis is needed.KHE may be accompanied by hemangioma or lymphangioma.Prognosis is affected by many factors and the comprehensive treatment is required.KMP should be remedied preferentially,individual treatment protocol and long term follow-up are necessary.

Induced transformation of rat oval cells line WB-F344 and tumor formation in NOD/SCID mice / 临床与实验病理学杂志

Purpose To study the malignant transformation after treating rat oval cell line ( WB-F344 ) with chemical carcinogen N-methyl-N′-nitro-N-nitrosoguanidine ( MNNG) . Methods WB-F344 cells were cultured with MNNG for severe times. The biological characteristics of induced cells were detected through the following methods:to check proliferation activity by flow cytometry analysis, to examine malignant transformation degree of induced cells by soft agar assay and tumor formation in NOD/SCID mice, and to investi-gate the transcriptional and protein levels of hepatocellular carcinoma marker GGT, GST-P by real time-PCR. Results Oval cells in-duced by MNNG showed changes in biological characteristics and malignant molecular markers. Conclusion Hepatic oval cells model is successfully established, which can be confirmed by tumor formation in NOD/SCID mice.

Atorvastatin attenuates parathyroid hormone 1-34 induced cardiomyocytes hypertrophy through downregulating K-Ras-ERK1/2 pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of atorvastatin on parathyroid hormone 1-34 (PTH1-34) induced neonatal rat cardiomyocytes hypertrophy and on the expression changes of small GTP-binding protein (K-Ras) and extracellular signal regulated protein kinases 1/2 (ERK1/2).</p><p><b>METHODS</b>Neonatal rat cardiomyocytes hypertrophy was established with 10(-7) mol/L rPTH1-34 in the presence or absence of 10(-5) mol/L atorvastatin or 10(-4) mol/L mevalonic acid (MVA). Cardiomyocyte diameter was measured by Motic Images Advanced 3.0 software, the synthetic rate of protein in cardiomyocytes was determined by (3)H-leucine incorporation and single-cell protein content was measured by BCA. The concentration of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by ELISA. Protein expression of ERK1/2, p-ERK1/2 and K-Ras was detected by Western blot.</p><p><b>RESULTS</b>Compared to PTH1-34 group, cellular diameter was decreased 12.07 µm, (3)H-leucine incorporation decreased 1622 cpm/well and single-cell protein content decreased 84.34 pg, ANP or BNP concentration reduced 7.13 µg/L or 20.04 µg/L, protein expression of K-Ras, ERK1/2 or p-ERK1/2 downregulated 0.81, 0.19 and 1.44 fold, respectively, in PTH1-34 plus atrovastatin co-treated cardiomyocytes (all P < 0.05). Compared to PTH1-34 plus atrovastatin co-treated group, cardiomyocyte diameter increased 4.95 µm, (3)H-leucine incorporation increased 750 cpm/well and single-cell protein content increased 49.08 pg, ANP or BNP increased 3.12 µg/L or 9.35 µg/L and protein expression of K-Ras, ERK1/2 or p-ERK1/2 upregulated 0.52, 0.06 and 1.19 fold (all P < 0.05) in MVA, PTH1-34 and atrovastatin co-treated cardiomyocytes.</p><p><b>CONCLUSIONS</b>Atrovastatin attenuates PTH1-34 induced neonatal rat cardiomyocytes hypertrophy through downregulating K-Ras and ERK1/2 pathway.</p>