Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Neutralization of interleukin-6 alleviates acute liver injury in mice].

Objective: To study the role of interleukin 6 (IL-6) in the occurrence and development of acute liver injury. Methods: Twelve C57BL/6 male mice without specific pathogens were randomly divided into a control group and an acute liver injury model group, with six mice in each group. Control and model group were injected with an equal volume (dosage of 10 mg/kg) of phosphate-buffered saline (PBS) and concanavalin A (ConA) into the tail vein, respectively. Samples were collected at 6 h for liver HE staining. Transaminase assay was used to determine the success of the induction model. The expression of IL-6, IL-17, IL-1ß, interferon (IFN) γ and tumor necrosis factor α were screened by quantitative fluorescence PCR (qPCR). The expressional condition of IL-6 and IFNγ were measured by enzyme-linked immunosorbent assay (ELISA). Subsequently, three control groups and three IL-6 neutralizing antibody groups were established for acute liver injury, respectively. Equal volumes of PBS or IL-6 neutralizing antibody (100 µg/body) were injected prior 30 minutes, followed by injection of ConA (10 mg/kg) into the tail vein. Blood sampled from eye and liver tissue were fetched at 6 h. Liver tissues were stained with HE and serum alanine aminotransferase (ALT) was determined. An independent sample T-test was used for data comparison. Results: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the model group was significantly higher than control group [ALT: (2 618.99 ± 188.08) U/L and (43.34 ± 5.02) U/L, t = -13.69, P = 0.001; AST: (942.48 ± 150.44) U/L and (57.80 ± 4.84) U/L, t = -5.878, P = 0.01]. Liver HE staining showed that the structure of hepatocyte cord was disordered, the cytoplasm of hepatocyte was lightly stained, and large necrotic foci were gradually formed, accompanied by lymphocyte infiltration, and then a mouse model of acute liver injury was successfully established. Protein levels of IL-6 and IFN, and mRNA of the model group were significantly up-regulated, as compared to control group. IL-6 mRNA expression of the model group was increased 73.7 times that of the control group (t =-6.218, P < 0.001), and the serum IL-6 expression level was also higher than that of the control group (18 537.02 ± 92.57) pg/ml (t = -199.782, P < 0.001). IFNγ mRNA was 108.4 times higher than that of the control the group (t = -4.413, P = 0.003), and serum IFNγ concentration of the model group was also higher than the control group (12 068.30 ± 288.43) pg/ml (t = -41.748, P < 0.001). Among them, IL-6 level was obviously increased, suggesting that it could participate in the occurrence and development of liver injury. IL-6 neutralizing antibody was injected into the tail vein. ALT level of IL-6 neutralizing antibody was significantly lower than acute liver injury control group [(167.41 ± 47.80) U/L and (1 520.34 ± 190.21) U/L, t = 6.899, P = 0.015]. Liver tissue HE staining showed that hepatocyte necrosis and the number of necrotic foci was significantly alleviated after blocking serum IL-6.Immunohistochemical results showed that the expression of activated caspase3 and hepatocyte apoptosis in the IL-6 neutralizing antibody group was decreased. Conclusion: Neutralizing IL-6 can significantly reduce acute liver injury caused by concanavalin A.

LINC01535 promotes proliferation and inhibits apoptosis in esophageal squamous cell cancer by activating the JAK/STAT3 pathway.

OBJECTIVE: To detect the expression of long intergenic non-coding ribonucleic acid (LINC) 01535 in esophageal squamous cell cancer (ESCC) tissues and cells, and to investigate the influences of LINC01535 on the proliferation and apoptosis of ESCC cells and the possible mechanism. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of LINC01535 in 43 cases of ESCC tissues and human esophageal cancer cells (KYSE30, EC9706, TE-13, and Ecal09) compared with human esophageal mucosal epithelial cells (HET-1A). The esophageal cancer cells with the highest expression were selected and transfected with small interfering RNA (si)-LINC01535 (experimental group) or si-negative control (NC) (control group). The interference efficiency was measured via qRT-PCR assay. Regulatory effects of LINC01535 on cell proliferative capacity was examined through colony formation assay and cell proliferation assay [Cell Counting Kit-8 (CCK-8)]. Cell cycle and apoptosis influenced by LINC01535 were detected via flow cytometry. Western blotting was applied to determine the expression changes in the molecular markers of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. RESULTS: LINC01535 expression in ESCC tissues and cells was remarkably higher than that in para-carcinoma tissues and esophageal mucosal epithelial cells. Knockdown of LINC01535 decreased proliferative capacity, arrested cell cycle in G1/G0 phase, and increased apoptotic rate of ESCC cells. The expressions of the molecular markers of the JAK/STAT3 signaling pathway were altered after knockdown of LINC01535. The above results illustrated that LINC01535 accelerated the proliferation but repressed the apoptosis of ESCC cells by regulating the JAK/STAT3 signaling pathway. CONCLUSIONS: The expression of LINC01535 is up-regulated in ESCC tissues and cells, and the highly expressed LINC01535 promotes the proliferation and inhibits the apoptosis of ESCC cells by regulating the JAK/STAT3 signaling pathway. Our findings provide new directions for the diagnosis and treatment of esophageal cancer.

[Changes and clinical significance of γδT cells in peripheral blood of patients with chronic hepatitis B during pegylated interferon α-2a treatment].

Objective: To observe the changes of γδT cells in the peripheral blood of patients with chronic hepatitis B (CHB) during pegylated interferon α-2a treatment, and to analyze the correlation between clinical indicators and curative effects. Methods: Peripheral blood of hepatitis B e antigen (HBeAg)-positive CHB patients were collected at different time points of Peg-IFNα-2a treatment, including 17 patients at 0 weeks, 20 patients at 12 weeks, 20 patients at 24 weeks, and 16 patients at 48 weeks. From these 11 patients, blood samples were frequently observed at 0, 12, 24, and 48 weeks of treatment. The frequencies of γδT and its subpopulation cells Vδ1T, Vδ2T, effector memory γδT (γδTem), central memory γδT (γδTcm), initial γδT (γδTnaive) and terminal differentiation effect γδT (γδTeff) cells in peripheral blood were detected by flow cytometry. Liver function, serum HBV markers and HBV DNA levels were measured simultaneously. SPSS 23.0 statistical software was used to analyze the differences in cell proportions at each treatment time point, and the correlation between cell proportions and alanine aminotransferase (ALT), HBsAg, HBeAg or HBV DNA levels. In addition, the correlation between the proportions of γδT and its subpopulation cells and the response to Peg-IFNα-2a treatment in the 11 patients with continuous follow-up were analyzed. Results: The percentage of γδT and Vδ2T cells in peripheral blood of patients with CHB decreased gradually during the period of 0-48 weeks of Peg-IFNα-2a treatment. The percentages of γδT cells and Vδ2T cells at 48 weeks were 6.89% (5%, 8.15%), 4.61% (2.16%, 6.50%), respectively; significantly lower than the 0 week [12.5% ​​(7.73%, 19%), 6.59% (3.86%, 13.62%)], the differences were statistically significant (P < 0.05). The proportions of Vδ1T, γδTem, γδTcm, γδTnaive, or γδTeff subpopulations were not statistically different at each time points (all P > 0.05). At the same time, the levels of ALT, HBsAg, HBeAg or HBV DNA were positively correlated with the ratio of γδT or Vδ2T cells (P < 0.05). Among the 11 patients with continuous followed- up, the proportion of γδTem cells in responders was significantly lower than that of non-responders at each time points, and the difference was statistically significant (P < 0.05). There was no statistically significant difference between the two groups (all P > 0.05). Conclusion: The proportion of γδT cells in the course of CHB treatment with Peg-IFNα-2a reduces the liver inflammation by decreasing the replication of HBV virus. Chronic hepatitis B patients with a lower proportion of effector memory (γδTem) cells may be more likely to get better response with Peg-IFNα-2a.

[Prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China].

Objective: The purpose of this study was to investigate the prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China. Methods: A total of 20 194 participants aged ≥18 years were selected randomly by cluster sampling from two townships(towns)in Henan Province from July to August 2007 and July to August 2008. Investigations included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination at baseline. A total of 16 155 participants were followed up from July to August 2013 and July to October 2014. Overall, 13 869 participants were included in the study, after excluding 2 286 participants with incomplete dyslipidemia follow-up data. Distributions of the characteristics of dyslipidemia were determined, and prevalence was standardized by age according to data of the 2010 Sixth National Population Census. Risk factors for dyslipidemia were analyzed using a logistic regression model after adjusting for sex, age, education level, marital status, and income status. Results: The prevalence of dyslipidemia was 53.72%(7 450/13 869)for residents aged ≥22 years living in rural areas of Henan Province(59.32%(3 069/5 174)for men and 50.39%(4 381/8 695)for women). The adjusted prevalence of dyslipidemia was 50.50%(59.27% for men and 45.53% for women). The prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C, and high LDL-C was 4.34%(602/13 868), 20.42%(2 826/13 837), 42.75%(5 927/13 865), and 3.14%(420/13 375), respectively, and the adjusted prevalence was 2.44%, 18.84%, 41.42%, and 1.86%, respectively. Logistic regression analyses showed that alcohol consumption(OR=1.27, 95% CI: 1.05-1.53), family history of hyperlipidemia(OR=1.29, 95% CI: 1.17-1.43), overweight(OR=1.40, 95% CI: 1.22-1.61), obesity(OR= 1.65, 95% CI: 1.39- 1.96), abnormal waist circumference(OR=1.22, 95% CI: 1.04- 1.43), and abnormal waist-height ratio(OR=1.21, 95% CI: 1.01-1.45)were significant independent risk factors, and high levels of physical activity(OR=0.85, 95% CI: 0.77- 0.95)and underweight(OR=0.52, 95% CI: 0.36- 0.75)were protective factors for dyslipidemia after adjusting for sex, age, education level, marital status, and income status. Conclusion: The prevalence of dyslipidemia was very high for this rural population. Alcohol consumption, family history of hyperlipidemia, overweight, obesity, abnormal waist circumference, and abnormal waist-height ratio were significant independent risk factors for dyslipidemia.

[Oxidative stress and antioxitant therapy of chronic periodontitis].

Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.

[Body mass index, waist circumference and waist-to-height ratio associated with the incidence of type 2 diabetes mellitus: a cohort study].

OBJECTIVE: To investigate the association between body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and the incidence risk of type 2 diabetes mellitus (T2DM). METHODS: In total, 20 194 participants ≥18 years old were selected randomly by cluster sampling from two township (town) of the county in Henan province from July to August of 2007 and July to August of 2008 and the investigation included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination were performed at baseline; 17 236 participants were enrolled in this cohort study. 14 720 (85.4%) were followed up from July to August 2013 and July to October 2014. Finally, 11 643 participants (4 301 males and 7 342 females) were included in this study. Incidence density and Cox proportional hazards regression models were used to evaluate the risk of T2DM associated with baseline BMI, WC, WHtR, and their dynamic changes. RESULTS: After average of 6.01 years following up for 11 643 participants, 613 developed T2DM and the incidence density was 0.89 per 100 person-years. After adjusted for baseline sex, age, smoking, drinking, family history of diabetes, as well as the difference of fasting plasma-glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP) between baseline and follow-up, Cox Proportional-Hazards regression analysis indicated that T2DM risk of baseline BMI overweight group, BMI obesity group, abnormal WC group and abnormal WHtR group were significantly higher than that of the corresponding baseline normal groups , and the incidence risk of T2DM reached the highest for those whose baseline BMI, WC and WHtR were all abnormal, the corresponding HR (95%CI) were 2.05 (1.62-2.59), 3.01 (2.33-3.90), 2.34 (1.89-2.90), 2.88 (2.21-3.74), 3.32 (2.50-4.40), respectively. Whether baseline BMI/WC was normal or not, T2DM risk increased if baseline WHtR was abnormal, and the HR (95%CI) of baseline normal BMI/abnormal WHtR group, baseline abnormal BMI/abnormal WHtR group, baseline normal WC/abnormal WHtR group, baseline abnormal WC/abnormal WHtR group were 1.88 (1.29-2.74), 3.08 (2.34-4.05), 2.15(1.53-3.00), 3.22 (2.45-4.23), respectively. The analysis for dynamic changes of BMI, WC, and WHtR indicated that in baseline normal WC or WHtR group, T2DM risk increased when baseline normal WC or WHtR developed abnormal at follow-up, and the corresponding HR (95%CI) were 1.79 (1.26-2.55), 2.12(1.32-3.39), respectively. In baseline abnormal WC or WHtR group, T2DM risk decresed when baseline abnormal WC or WHtR reversed to normal at follow-up, and the corresponding HR (95%CI) were 2.16 (1.42-3.29), 2.62 (1.63-4.20), respectively. CONCLUSION: BMI, WC, and WHtR were associated with increased T2DM risk. The more abnormal aggregation of BMI, WC, and WHtR presents, the higher T2DM risk was. T2DM risk could be decreased when abnormal WC or WHtR reversed to normal.

Hrd1 facilitates tau degradation and promotes neuron survival.

Intraneuronal accumulation of abnormal phosphorylated tau (p-tau) is a molecular pathology in many neurodegenerative tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17). However, the underlying mechanism remains unclear. Here, we showed an inverse relationship between endoplasmic reticulum membrane ubiquitin ligase (E3) Hrd1 expression and p-tau accumulation in the hippocampal neurons of AD, and proposed that Hrd1 may be a negative regulator of p-tau. This notion was further supported by in vitro study demonstrating that Hrd1 interacted with tau and promoted the degradation of total tau and p-tau as well. The degradation of tau depended on its Hrd1 E3 activity. Knockdown of endogenous Hrd1 with siRNA stabilized tau levels. In addition, inhibition of proteasome maintained tau level and increased Hrd1-mediated tau ubiquitination, suggesting the proteasome was involved in tau/p-tau degradation. Over-expression of Hrd1 significantly alleviated tau cytotoxicity and promoted cell survival. These results indicated that Hrd1 functions as an E3 targeting tau or abnormal p-tau for proteasome degradation. The study provides an important insight into the molecular mechanisms of human tauopathies.

Formation and structural anomaly of the metastable phases in an immiscible Ag-Mo system studied by ion beam mixing and molecular dynamics simulation.

For the equilibrium immiscible Ag-Mo system characterized by a large positive heat of formation, the nanosized Ag-Mo multilayered samples are designed and prepared to include sufficient interfacial free energy to elevate their initial energetic states to be higher than that of either the amorphous phase or solid solution and then subject to 200 keV xenon ion irradiation. The results show that a uniform amorphous alloy can be obtained within a composition range, at least, from 25 to 88 atom % of Mo. Interestingly, in the intermediate stage of ion irradiation, a bcc phase, an amorphous phase, and an order (bcc)-disorder coexisting state appear simultaneously in the Ag12Mo88 multilayered sample and extend over the entire bright field image with unanimously homogeneous composition. In thermodynamic modeling, a Gibbs free energy diagram of the Ag-Mo system is constructed, based on Miedema's model, and suggests that within a narrow composition regime of 85-90 atom % of Mo, the energy difference between the bcc and the amorphous phases is extremely small, which is probably the very reason for the order-disorder coexisting state to appear. In atomistic modeling, an ab initio derived Ag-Mo potential is applied to perform molecular dynamics simulations. The simulations not only determine an intrinsic glass-forming ability/range (GFA/GFR) of the Ag-Mo system to be from 10 to 88 atom % of Mo but also reveal the possibility of the formation/appearance of a crystalline and amorphous mixture in a narrow composition regime of 88-92 atom % of Mo. Apparently, the theoretical results are in excellent agreement and/or compatible with the experimental observations in ion beam mixing.

Formation of amorphous alloys by ion beam mixing and its multiscale theoretical modeling in the equilibrium immiscible Sc-W system.

Unique amorphous alloys are synthesized at the compositions of 25 and 40 atom % of W by ion beam mixing in the equilibrium immiscible Sc-W system characterized by a positive heat of formation of +14 kJ/mol. In thermodynamic modeling, a Gibbs free energy diagram is constructed based on Miedema's theory, and the diagram predicts a glass-forming range of the Sc-W system to be within 12-58 atom % of W. To develop an atomistic model, ab initio calculations are first conducted to assist the construction of an n-body Sc-W potential under the embedded atom method. The proven realistic potential is applied in molecular dynamic simulations to study the crystal-to-amorphous transition in the Sc-W solid solutions, thus determining the glass-forming ability of the system to be within 15-50 atom % of W. Apparently, both theoretical predicted glass-forming ranges cover the experimentally measured one, showing an excellent agreement. We report, in this paper, the experimental results from ion beam mixing and the multiscale theoretical modeling concerning the amorphous alloy formation in the Sc-W system together with a brief discussion of the structural transition mechanism.

The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25-35 in middle-aged rats.

This work investigated the ability of melatonin to prevent oxidative damage in brain tissue induced by injection of beta-amyloid peptide 25-35 (Abeta25-35) in middle-aged rats. The Morris water maze was used to evaluate the cognitive function of the rats. Thiobarbituric acid-reactive substances and antioxidative enzymes (superoxide dismutase and glutathione peroxidase) activities were measured. It was found that injection of (Abeta25-35) (20 microg) into the rat hippocampus caused an increase in the latency (the time to find the platform), the total swimming distance to the platform, and the starting angles in (Abeta25-35)-treated rats. Furthermore, a significant rise in lipid peroxidation and decrease in antioxidative enzyme activities in brain tissue were found. Melatonin (0.1, 1, and 10 mg/kg, i.g. x 10 days) improved the spatial resolution of amnesic rats in the Morris water maze test. Meanwhile, melatonin antagonized the lipid peroxidation in both the mitochondria (P < 0.01) at the doses of 0.1, 1.0, and 10 mg/kg and in the cytoplasm at the doses of 0.1 and 1.0 mg/kg. Also in the amnesic rats, melatonin (0.1, 1.0, and 10 mg/kg. i.g. x 10 days) stimulated the antioxidative enzyme activities. The results show that melatonin effectively reduced lipid peroxidation and enhanced the antioxidative enzyme activities in Abeta(25-35)-treated rats, which may contribute to the improvement of rats' learning and memory impaired by Abeta(25-35).

Improvement of melatonin to the learning and memory impairment induced by amyloid beta-peptide 25 - 35 in elder rats.

AIM: To investigate improvement of melatonin on learning and memory impairment induced by amyloid beta-peptide 25 - 35 (Abeta25-35) in elder rats. METHODS: Step-down type passive avoidance test, shuttle-box test, and Morris water maze were used together to determine effects of Abeta25-35 and melatonin on learning and memory. Pathological changes were observed by HE, Congo red, and Ag staining. RESULTS: The elder rats were injected bilaterally Abeta25-35 20 microg into the hippocampus to induce learning and memory dysfunction. Melatonin administration (0.1, 1, and 10 mg/kg, ig x 8 d) to the Abeta25-35-treated rats prolonged the latency, shortened the total stimulating time, and decreased the number of errors in the step-down test. Shuttle-box test showed that melatonin improved amnesic rats' performance at the same doses. Melatonin (0.1, 1, and 10 mg/kg ), giving for 10 d, could enhance the spatial resolution of amnesic rats in Morris water maze test. Also in Abeta25-35-treated group, a decrease in the number of neurons in cortex and hippocampus, a massive glial reaction, and neurophilic phenomenon were detected by HE staining; the positive vascular amyloidosis by Congo red and fibrils by Ag staining were observed. Melatonin (0.1 and 1 mg/kg)could inhibit above pathological changes in Abeta25-35 group. CONCLUSION: Melatonin improved the impaired learning and memory induced by Abeta25-35 in elder rats.

[Expression of Bacillus thuringiensis (Bt) crystal toxin gene in the chloroplast of tobacco].

The 3.5 kb wild-type Bt Cry I A(c) gene and its 3' truncated forms (2.1 kb, 1.8 kb) were placed under the control of plastid expression signals consisting of the strong light-induced psbA promoter and its 3' untranslated region with the aadA cassette (Prrn, aadA and psbA3') as a selectable marker. The resulting vectors pBT3, pBT8 and pBT22 also contain flanking tobacco plastid DNA homology regions to direct insertion of the Bt transgene into the tobacco plastid genome between psbA and trnK by homologous recombination. Transformed plastid genomes were selectively amplified by growing the cells on spectinomycin medium. Several independently transformed lines were obtained at last. The results of Southern and Western blot demonstrated that these three kinds of Bt genes had been introduced into tobacco plants, and their filial generations are resistant to spectinomycin. Insecticidal activity assay with transgenic tobacco leaves indicate that some plants have strong toxicity to cotton bollworm. This is the first report in China that Bt gene has been introduced and successfully expressed in the chloroplast of higher plants.

[Studies on the flavonoids from Dendranthema lavandulifolium].

From the whole plant of Dendranthema lavandulifolium, two flavonoides (I, II) and two flavone glycosides (III, IV) were isolated. They were identified as luteolin (I), apigenin (II), 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl(1-->6)-beta- D-glucopyranosyl (acaciin III) and 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl (1-->6) [2-O-acetyl-beta-D-glucopyranosyl(1-->2)]-beta-D-glucopyranoside (IV) by means of IR, UV, 1H-NMR, 13C-NMR, EI-MS, HRFAB, etc. Among these four compounds, I, II were isolated for the first time from this plant, IV is a new compound.

[Comparison of multiple dosage bioavailability between phenylpropanolamine controlled release suspension and conventional tablet in healthy volunteers].

Compared studies between the pharmacokinetics of phenylpropanolamine (PPA) controlled release suspension (CRS) and that of PPA conventional tablet in 10 healthy volunteers showed that the maximal plasma concentration (Cmax), the minimal plasma concentration (Cmin) and the fluctuation index (FI) values were 169.06 +/- 7.76 ng.ml-1, 82.80 +/- 4.29 ng/ml-1 and 0.20 +/- 0.04 respectively for PPA CRS, 180.5 +/- 8.91 ng.ml-1, 76.18 +/- 5.97 ng.ml-1 and 0.81 +/- 0.07 respectively for the conventional tablet. The Cmax and FI of PPA CRS were significantly lower compared with those of the conventional tablet (P < 0.01) during steady state. The Cmin of PPA CRS was higher than that of the conventional tablet (P < 0.05).

[Determination of cefixime in human plasma and urine using high performance liquid chromatography column switching technique].

A double column and double pump HPLC switching system is described for the analysis of cefixime in human plasma and urine. The system used muBondapak C18 short pretreatment column for on-line sample clean-up and a Hitachi GEL 3056 (ODS) analytical column for separation. A mixed solution of 0.01 mol/L H3PO4-0.1 mol/L KH2PO4-H2O (20:1:79) was used as the pretreatment mobile phase and CH2CH-0.01 mol/L H3PO4-0.1 mol/L KH2PO4-H2O (13:20:1:66) was used as analytical mobile phase. The compound in plasma and urine is detected by ultraviolet absorption at 286 nm and 314 nm, respectively. The absolute recoveries of the method in plasma and urine were 99.1% and 98.6% respectively. The relative standard deviations of the method are 0.70-3.82% and 0.80-3.73% in plasma, 1.53-3.08% and 1.31-2.67% in urine between days and day-to-day. Linear calibration curve for cefixime was measured over the range of 0.1-3.2 micrograms/ml in plasma and 1.0-32.0 micrograms/ml in urine, and the correlation coefficients were all 0.9999. The detection limit was 0.05 micrograms/ml in plasma and 0.2 micrograms/ml in urine. The plasma and urine samples were diluted with water and injected directly onto the HPLC system. The operation is simple and the relative sensitivity is markedly increased because of higher recoveries and larger loading capacity of the sample.

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. II. Morphologic, ultrastructural and histochemical changes of the cancer cells after intrarectal and intravenous 5-Fu administration].

From March 1981 to October 1985, 5-Fu was preoperatively given to 65 Dukes B and C rectal cancer patients (intrarectal suppository 40 and emulsion 20, intravenous 5). The results indicated that after intrarectal administration, marked changes and destruction of the cancer cells in morphology were observed in 40% of the resected rectal specimens for suppository and in 45% for emulsion; marked retrograde degeneration in ultrastructure was found in 47.5% for suppository and in 50% for emulsion; DNA synthesis was obviously reduced in 63% for suppository and in 75% for emulsion. It is suggested that the emulsion be a better preparation. No obvious changes or destruction in morphology and ultrastructure were observed in cancer cells treated by intravenous drip of high dose 5-Fu though leukopenia below 4000 was found in 2/5. However, it was 0/60 by rectal administration. This implies that the intrarectal route is more rational than the conventional intravenous route. This study presents an alternate supplementary treatment in addition to radiotherapy for the reduction of postoperative local recurrence of Dukes B and C rectal cancers.

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. I. Concentration and distribution of 5-Fu in tissues monitored by 14C-isotopically tagged 5-Fu].

Experimental studies on more rational route and preparation of preoperative administration of 5-Fu were undertaken from March 1981 to June 1985. The experimental observation shows that intrarectal administration of radioisotope 14C tagged 5-Fu (suppository and emulsion) produces a much higher concentration in the rectal wall and mesenteric lymph nodes compared with its intravenous administration (40 rabbits) and produces a much higher concentration in cancer tissue than in surrounding tissues and in mesenteric lymph nodes than in the inferior mesenteric veins (4 patients). These findings favor the attenuation or destruction of cancer cells in the tumor and regional lymph nodes-the main route of spread. Also, after intrarectal administration of 14C tagged 5-Fu, its concentration in the lung, liver and bone marrow is much lower than that after intravenous administration (40 rabbits), and hence systemic toxicity is decreased. The above results indicate that the intrarectal route stands better than the conventional intravenous route for 5-Fu preoperative adjuvant chemotherapy in rectal cancer. Administration of 5-Fu emulsion produces a higher concentration in the rectal wall and mesenteric lymph nodes than that of 5-Fu suppository and peak concentration also appears earlier, i.e. 2 hours after the administration of 5-Fu emulsion. This will lessen the interference of 5-Fu absorption owing to its premature evacuation, indicating that emulsion is a better form for intrarectal 5-Fu.

Surgical treatment and late results in 1226 cases of colorectal cancer.

One thousand two hundred twenty-six cases of colorectal cancer were treated surgically between 1956 and 1978. Seven hundred ninety-eight cases (65.08 per cent) were rectal, 74.3 per cent of which were located extraperitoneally. Dukes' C2 cases and cases with distant metastasis constituted 39.15 per cent, and Dukes' A cases, 9.22 per cent. Resectability rate was 75.1 per cent (77.6 per cent for rectal cancer). Two hundred and four cases (32.96 per cent) of rectal excision were restorative resections. Of the combined excisions for extraperitoneal lesions in females, 84.8 per cent were posterior pelvic exenterations. The overall operative mortality rate was 2.93 per cent. The mortality rate for 921 cases of resection was 1.73 per cent, for rectal resection, 0.8 per cent, and for curative rectal resection, 0.63 per cent. The follow-up rate was 94.13 per cent. The five-and ten-year survival rates for rectal resection were 53.08 +/- 2.29 per cent and 47.65 +/- 2.44 per cent; for curative rectal resection. 66.91 +/- 2.54 per cent and 60.27 +/- 3.03 per cent; and for Dukes' A cases, 98.05 +/- 1.35 per cent and 96.39 +/- 2.13 per cent. The five-and ten-year survival rates for colonic resection were 59.79 +/- 2.04 per cent and 52.18 +/- 3.49 per cent; for curative colonic resection, 72.79 +/- 3.39 per cent and 62.06 +/- 4.17 per cent; and for Dukes' A cases, both 100 per cent. Besides the extent of spread and degree of malignancy of a lesion, the local immunologic reaction of the host is also important in prognosis. The more lymphocytic infiltration in and around the cancer, the more follicular hyperplasia and sinus histiocytosis in regional lymph nodes, the better is the prognosis. The problem of anal preservation in radical resection of rectal cancer and the problem of improvement of results in the treatment of extraperitoneal rectal cancer are discussed in detail.