Randomized clinical trial of continuous transversus abdominis plane block, epidural or patient-controlled analgesia for patients undergoing laparoscopic colorectal cancer surgery.

BACKGROUND: The optimal analgesia regimen after laparoscopic colorectal cancer surgery is unclear. The aim of the study was to characterize the beneficial effects of continuous transversus abdominis plane (TAP) blocks initiated before operation on outcomes following laparoscopic colorectal cancer surgery. METHODS: Patients undergoing surgery for colorectal cancer were divided randomly into three groups: combined general-TAP anaesthesia (TAP group), combined general-thoracic epidural anaesthesia (TEA group) and standard general anaesthesia (GA group). The primary endpoint was duration of hospital stay. Secondary endpoints included gastrointestinal motility, pain scores and plasma levels of cytokines. RESULTS: In total, 180 patients were randomized and 165 completed the trial. The intention-to-treat analysis showed that duration of hospital stay was significantly longer in the TEA group than in the TAP and GA groups (median 4·1 (95 per cent c.i. 3·8 to 4·3) versus 3·1 (3·0 to 3·3) and versus 3·3 (3·2 to 3·6) days respectively; both P < 0·001). Time to first flatus was earlier in the TAP group (P < 0·001). Visual analogue scale (VAS) scores during coughing were lower in the TAP and TEA groups than the GA group (P < 0·001). Raised plasma levels of vascular endothelial growth factor C, interleukin 6, adrenaline and cortisol were attenuated significantly by continuous TAP block. CONCLUSION: Continuous TAP analgesia not only improved gastrointestinal motility but also shortened duration of hospital stay. A decreased opioid requirement and attenuating surgical stress response may be potential mechanisms. Registration number: ChiCTR-TRC-1800015535 ( http://www.chictr.org.cn).

ANTECEDENTES: El régimen analgésico óptimo para los pacientes tras cirugía laparoscópica del cáncer colorrectal se desconoce. El objetivo de este estudio fue caracterizar los efectos beneficiosos del bloqueo continuo del plano transverso abdominal (transversus abdominis plane, TAP) iniciado preoperatoriamente sobre los resultados después de cirugía laparoscópica del cáncer colorrectal. MÉTODOS: Los pacientes sometidos a cirugía del cáncer colorrectal fueron divididos aleatoriamente en tres grupos: anestesia combinada general-TAP (grupo TAP), anestesia epidural combinada general-torácica (grupo TEA) y anestesia general estándar (grupo GA). El resultado primario fue la duración de la estancia hospitalaria. Los resultados secundarios incluyeron la motilidad gastrointestinal, puntuaciones de dolor y niveles plasmáticos de citocinas. RESULTADOS: En total, 180 pacientes fueron aleatorizados y 165 completaron el ensayo. El análisis por intención de tratar mostró que la duración de la estancia hospitalaria en el grupo TEA fue significativamente más larga que en el grupo TAP y GA respectivamente (4,1 (3,8-4,3) versus 3,1 (3,0-3,3) días, P < 0,001; 4,1 (3,8-4,3) versus 3,3 (3,2-3,6) días, P < 0,001). El tiempo hasta la primera eliminación de gases fue más precoz en el grupo TAP (P < 0,001). Las puntuaciones de la escala analógica visual (visual analogue scale, VAS) durante la tos en el grupo TAP y TEA fueron inferiores (P < 0,01). Los niveles elevados en plasma del factor de crecimiento endotelial C (VEGF-C), interleucina (IL)-6, epinefrina y cortisol fueron atenuados significativamente por el bloque TAP continuo. CONCLUSIÓN: La analgesia TAP continua no solo mejora la motilidad gastrointestinal, sino que también acorta la estancia hospitalaria. Una disminución en los requerimientos de opiáceos y la atenuación de la respuesta al estrés quirúrgico podrían ser mecanismos potenciales de la acción de TAP.

Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer: a meta-analysis based on Chinese patients.

BACKGROUND: Colorectal carcinoma is one of most diagnosed solid malignant carcinoma. The chemotherapy combined with target drugs in the treatment of advanced colorectal cancer in not conclusive. METHODS: The clinical studies reporting the activity and adverse events between chemotherapy alone versus chemotherapy combined with anti-epidermal growth factor receptor drugs were screened in the databases of Medline, the Cochrane Library, Wanfang and CNKI and included in this meta-analysis. The risk ratio (RR) and its 95% confidence interval (CI) for treatment response and adverse events were pooled by random or fixed effect model. RESULTS: A total of 10 clinical studies reporting chemotherapy combined with the target in the treatment of advanced colorectal cancer were included in this study. The pooled RR was 3.26 (95% CI: 1.74-6.11, P < 0.05), 1.49 (95% CI: 1.23-1.80) and 1.65 (95% CI: 1.37-1.98) for complete response (CR), partial response and objective response rate, respectively. For nausea and vomiting events, the RR was 1.62 (95% CI: 1.33-1.97, P < 0.05) indicating higher incidence of nausea and vomiting was observed in the combined group compared with chemotherapy alone. However, the diarrhea (RR = 1.10, 95% CI: 0.86-1.42, P > 0.05), liver function damage (RR = 1.03, 95% CI: 0.74-1.42), myelosuppression (RR = 1.04, 95% CI: 0.83-1.31) and neurotoxicity (RR = 1.12, 95% CI: 0.93-1.35) were not different between the two groups. CONCLUSION: For Chinese patients with advanced colorectal cancer, chemotherapy combined with target drug can improve the response rate, but also increase the risk of nausea and vomiting.

Genetic analysis and molecular mapping of maize (Zea mays L.) stalk rot resistant gene Rfg1.

One single pathogen Fusarium graminearum Schw. was inoculated to maize inbred lines 1,145 (Resistant) and Y331 (Susceptive), and their progenies of F(1), F(2) and BC(1)F(1) populations. Field statistical data revealed that all of the F(1) individuals were resistant to the disease and that the ratio of resistant plants to susceptive plants was 3:1 in the F(2) population, and 1:1 in the BC(1)F(1 )population. The results revealed that a single dominant gene controls the resistance to F. graminearum Schw. The resistant gene to F. graminearum Schw. was denominated as Rfg1 according to the standard principle of the nomenclature of the plant disease resistant genes. RAPD (randomly amplified polymorphic DNA) combined with BSA (bulked segregant analysis) analysis was carried out in the developed F(2) and BC(1)F(1 )populations, respectively. Three RAPD products screened from the RAPD analysis with 820 Operon 10-mer primers showed the linkage relation with the resistant gene Rfg1. The three RAPD amplification products (OPD-20(1000), OPA-04(1100) and OPY-04(900)) were cloned and their copy numbers were determined. The results indicated that only OPY-04(900) was a single-copy sequence. Then, OPY-04(900) was used as a probe to map the Rfg1 gene with a RIL F(7) mapping population provided by Henry Nguyen, which was developed from the cross "S3xMo17". Rfg1 was primarily mapped on chromosome 6 between the two linked markers OPY-04(900) and umc21 (Bin 6.04-6.05). In order to confirm the primary mapping result, 25 SSR (simple sequence repeat) markers and six RFLP (restriction fragment length polymorphism) markers in the Rfg1 gene-encompassing region were selected, and their linkage relation with Rfg1 was analyzed in our F(2) population. Results indicated that SSR marker mmc0241 and RFLP marker bnl3.03 are flanking the Rfg1 gene with a genetic distance of 3.0 cM and 2.0 cM, respectively. This is the first time to name and to map a single resistant gene of maize stalk rot through a single pathogen inoculation and molecular marker analysis.

Molecular tagging and genetic mapping of the disease resistance gene RppQ to southern corn rust.

Southern corn rust (SCR), Puccinia polysora Underw, is a destructive disease in maize ( Zea mays L.). Inbred line Qi319 is highly resistant to SCR. Results from the inoculation test and genetic analysis of SCR in five F(2) populations and five BC(1)F(1 )populations derived from resistant parent Qi319 clearly indicate that the resistance to SCR in Qi319 is controlled by a single dominant resistant gene, which was named RppQ. Simple sequence repeat (SSR) analysis was carried out in an F(2) population derived from the cross "Qi319x340". Twenty SSR primer pairs evenly distributed on chromosome10 were screened at first. Out of them, two primer pairs, phi118 and phi 041, showed linkage with SCR resistance. Based on this result, eight new SSR primer pairs surrounding the region of primers phi118 and phi 041 were selected and further tested regarding their linkage relation with RppQ. Results indicated that SSR markers umc1,318 and umc 2,018 were linked to RppQ with a genetic distance of 4.76 and 14.59 cM, respectively. On the other side of RppQ, beyond SSR markers phi 041 and phi118, another SSR marker umc1,293 was linked to RppQ with a genetic distance of 3.78 cM. Because the five linkage SSR markers (phi118, phi 041, umc1,318, umc 2,018 and umc1,293) are all located on chromosome 10, the RppQ gene should also be located on chromosome 10. In order to fine map the RppQ gene, AFLP (amplified fragment length polymorphism) analysis was carried out. A total 54 AFLP primer combinations were analyzed; one AFLP marker, AF1, from the amplification products of primer combination E-AGC/M-CAA, showed linkage with the RppQ gene in a genetic distance of 3.34 cM. Finally the RppQ gene was mapped on the short arm of chromosome 10 between SSR markers phi 041 and AFLP marker AF1 with a genetic distance of 2.45 and 3.34 cM respectively.

Fine mapping of the rice thermo-sensitive genic male-sterile gene tms5.

AnnongS-1, a thermo-sensitive genic male-sterile (TGMS) rice line, has a new TGMS gene. Genetic analysis indicated that the sterility of AnnongS-1 was controlled by a single resessive gene named tms5. In our previous studies based on an F(2) population from the cross between AnnongS-1 and Nanjing11, tms5 was mapped on chromosome 2. Recently, a RIL (recombinant inbred line) population from the same cross was developed and used for the fine mapping of the tms5 gene. Molecular marker techniques combined with BSA (bulked segregant analysis) were used. As a result, two AFLP markers (AF10, AF8), one RAPD marker (RA4), one STS marker (C365-1), one CAPs marker (G227-1) and four SSR markers (RM279, RM492, RM327, RM324) were found to be closely linked to tms5 gene. The DNA sequences of the RFLP marker of C365 and G227 were found in GenBank, and on the basis of these sequences, many primers were designed to amplify the two parents and their RIL population plants. Finally, the tms5 gene was mapped between STS marker C365-1 and CAPs marker G227-1 at a distance of 1.04 cM from C365-1 and 2.08 cM from G227-1.

[lambda N gene expression regulated by the leader sequence].

It was reported recently that changing the TIR (translational initiation region) of lambda N gene resulted in the increasing expression of lambda N gene and it was regulated at translational level. According to the alignment, the leader sequence of lambda N gene had three parts: a code region for ORF lambda N, the upstream sequence of ORF lambda N and 17 bp of spacer between ORF lambda N and downstream of lambda N gene. ORF lambda N is an open reading frame located at upstream of lambda N gene coding a peptide of 19 amino acids. To study the mechanism of regulation of lambda N gene expression, three serials of plasmids with mutant leader region of lambda N gene were constructed. (1) pMC1403-XT, in which the start codon or the partial code of ORF lambda N was connected with lacZ to obtain the ORF lambda N-lacZ fusion gene and in which the ORF lambda N-lacZ expression was under the control of a strong trp/lac promoter; (2) The ORF lambda N mutants in which the termination codon TAA was introduced into ORF lambda N at different positions by site-directed mutagenesis to preterminate the ORF lambda N on plasmid pMC1403N; (3) Mutants in which a deletion was located at upstream ORF lambda N in the ORF lambda N mutants above. The results obtained from determination of the beta-galactosidase activity in the transformants harboring the different plasmids showed that the ORF lambda N-lacZ expression was suppressed by the ORF lambda N code region and the lambda N expression was increased in both the second and third serials of mutants. At the same time the results from RNA-DNA dot hybridization showed that the lambda N gene expression was regulated at translational level. Therefore it was predicted that the reason of relatively low expression for lambda N gene in pMC1403N was due to the low efficiency of ORF lambda N translation. There are two ways to increase the expression of lambda N gene. One is to preterminate the translation of ORF lambda N at a suitable position to decrease the ORF lambda N effects on downstream lambda N gene translation; the other is to change the upstream sequence of ORF lambda N to improve its translation efficiency.

[AFLP analysis of photoperiod-sensitive genic male sterile(PGMS) rice mutant lines].

The reaction conditions for rice AFLP assay were optimized. The relative efficiencies for polymorphism detection of RFLP, RAPD and AFLP were compared through the analysis between a pair of PGMS allelic mutant lines(NK58S and NK58F). Results indicated that the efficiency for polymorphism detection in rice is in the order of AFLP > RAPD > RFLP, and also indicated that AFLP is a powerful DNA molecular marker technique for polymorphism detection, especially in the cases of extremely low polymorphism, such as isogeneic lines and allelic mutant lines. The advantages and disadvantages of these three molecular marker systems were discussed. Using AFLP in conjunction with bulked segregating analysis, 5106 AFLP loci were screened and 9 of them showed polymorphism between NK58S and NK58F, 4 of the polymorphic AFLP products were cloned, Southern bloting analysis showed that two of them were single copy sequences while the other two were low copy sequences in rice genome.

Structural role for a conserved region in the CTP synthetase glutamine amide transfer domain.

Site-directed mutations were introduced into a conserved region of the Escherichia coli CTP synthetase glutamine amide transfer domain. The amino acid replacements, valine 349 to serine, glycine 351 to alanine, glycine 352 to proline, and glycine 352 to cysteine, all increased the lability of CTP synthetase. The proline 352 replacement abolished the capacity to form the covalent glutaminyl-cysteine 379 catalytic intermediate, thus preventing glutamine amide transfer function; NH3-dependent CTP synthetase activity was retained. In CTP synthetase (serine 349), both glutamine and NH3-dependent activities were increased approximately 30% relative to that of the wild type. CTP synthetase mutants alanine 351 and cysteine 352 were not overproduced because of apparent instability and proteolytic degradation. We conclude that the conserved region between residues 346 and 355 in the CTP synthetase glutamine amide transfer domain has an important structural role.