Comparison of the efficacy and safety of the EC-T (epirubicin/cyclophosphamide followed by docetaxel) and TCb (docetaxel/carboplatin) neoadjuvant regimens in early TOP2A-normal stage II-III breast cancer.

This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1 + carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen. The primary endpoint was the ratio of RCB 0/1 (residual cancer burden 0/1) after neoadjuvant chemotherapy. The secondary endpoint was the safety of the two groups. There was no significant difference in the ratio of RCB 0/1 between the two groups (23% vs. 23.9%, p=0.614). Among the triple-negative breast cancer patients, the efficacy did not differ between the two groups (40% vs. 32%, p=0.52). Among the lymph node metastasis patients, the efficacy of the EC-T group was significantly better than that of the TCb group (14% vs. 2.6%, p=0.03). Regarding the side effects, the incidence of grade 3/4 anemia was higher in the EC-T group than in the TCb group (21.0% vs. 8.33%, p=0.002), while the incidence of grade 3/4 neutropenia was higher in the EC-T group than in the TCb group (17% vs. 14.44%, p=0.570), and the incidence of grade 3/4 thrombocytopenia was low in each group (EC-T group: 6 % and TCb group: 7.22%, p=0.697). In the EC-T group, grade 3/4 nausea and vomiting occurred in 5 patients. The EC-T group showed a higher rate of grade 3/4 myalgia than the TCb group (7% and 4.44%, respectively, p=0.363). To conclude, the TCb regimen can be used as an alternative regimen for TOP2A-normal stage II-III breast cancer patients in neoadjuvant chemotherapy. However, in patients with node-positive tumors, EC-T is still recommended. Though no difference of grade 3/4 thrombocytopenia in two groups, grade 4 thrombocytopenia caused by the carboplatin-containing regimen should be taken seriously.

Is the optimal intervention policy UC superior to the suboptimal policy MFPT over inferred probabilistic Boolean network models?

A salient problem in translational genomics is the use of gene regulatory networks to determine therapeutic intervention strategies. Theoretically, in a complete network, the optimal policy performs better than the suboptimal policy. However, this theory may not hold if we intervene in a system based on a control policy derived from imprecise inferred networks, especially in the small-sample scenario. In this paper, we compare the performance of the unconstrained (UC) policy with that of the mean-first-passage-time (MFPT) policy in terms of the quality of the determined control gene and the effectiveness of the policy. Our simulation results reveal that the quality of the control gene determined by the robust MFPT policy is better in the small-sample scenario, whereas the sensitive UC policy performs better in the large-sample scenario. Furthermore, given the same control gene, the MFPT policy is more efficient than the UC policy for the small-sample scenario. Owing to these two features, the MFPT policy performs better in the small-sample scenario and the UC policy performs better only in the large-sample scenario. Additionally, using a relatively complex model (gene number N is more than 1) is beneficial for the intervention process, especially for the sensitive UC policy.

[Study of ultrasonographic features in predicting reginal lymph node metastasis in patients with papillary thyroid carcinoma].

OBJECTIVE: To demonstrate the ultrasonographic features of papillary thyroid carcinoma (PTC) in predicting associated cervical lymph nodes metastasis (LNM). METHODS: A total of 136 patients diagnosed with PTC in Beijing Tongren Hospital between January 2014 and September 2014 were enrolled.Of 136 cases, forty patients were confirmed with cervical lymph node metastasis.Seven were males, 33 were females, aged from 18 to 65 years old, mean age was (39.6±10.3) years .The remaining 96 were reported without lymph node metastasis.Twenty-one were males, 75 were females, aged from 23 to 86 years old, mean age was (47.7±12.8) years.Medical record was reviewed for demographic characteristics and pathological findings.The ultrasonographic features of each case were evaluated retrospectively.The difference of ultrasonographic features between the patients with and without LNM was examined. RESULTS: There were 178 PTCs confirmed with pathology, 159 lesions (89.3%) were detected by ultrasonography, the remaining 19 lesions (10.7%) were under-detected.Of 136 patients with PTC, 40 cases (40/136, 29.4%) were confirmed with cervical LNM, while the remaining 96 cases (96/136, 70.6%) were determined without cervical LNM.PTC with cervical LNM was more frequently seen in the patients who were younger (P=0.000 5) and presenting with multifocal tumors (P=0.014 6). Ultrasonographic features of PTC which significantly associated with LNM were ill-defined margins (P=0.018), solid appearance (P=0.003), and presence of calcification (P=0.000). Of 40 cases with LNM, central cervical LNM was seen in 32 cases (80%), 72.5% of whom appeared as unilateral distribution. CONCLUSIONS: Patients diagnosed with PTC with younger age and identified with multiple foci of tumors at the time of diagnosis are in an increased risk of associated cervical LNM.Ultrasonographic features of ill-defined margins, solid appearance and calcification in PTC are significant predictors of LNM.

Effect of the IkBα mutant gene delivery to mesenchymal stem cells on rat chronic pancreatitis.

This study aimed to investigate the effect of inhibitors of the NF-kΒ alpha mutant gene (IkBaM) delivery to mensenchymal stem cells (MSCs) on rat chronic pancreatitis (CP). A total of 120 Sprague-Dawley rats were randomly divided into 6 groups of 20: Group A was injected with sterile saline solution, Group B was injected with allogenic MSCs, Group C1 was injected with allogenic IkBαM-MSCs cultured in vitro 4 h before CP modeling, Group C2 was injected with allogenic IkBαM-MSCs cultured in vitro during CP modeling, Group C3 was cultured with allogenic IkBαM-MSCs cultured in vitro 4 h after CP modeling, and Group D was injected with rAAV2-MSCs. Cytokine levels of ICAM-1, CTGF, IL-1, IL-6, IL-8, TNF-α, TIMP-1, TIMP-2, IL-10, FN, MMP-1, MMP-2, MMP-3, and MMP-9 were examined. The results indicated that allogenic IκBαM-MSCs could reduce pro-inflammatory cytokine levels and increase anti-inflammatory cytokine levels in CP. The allogenic IkBαM-MSCs reduced the activation and promoted the apoptosis of pancreatic stellate cells in the rat model of CP. IkBαM-MSCs influenced the proliferation and apoptosis of pancreatic stellate cells by regulating the activation of the PPAR, MAPK, mTOR, TGF-ß, NOD-like receptor, Notch, WNT, TGF-ß1-SMAD-2/3, and P53 signal transduction pathways.

Multiplex PCR for the simultaneous identification and detection of Meloidogyne incognita, M. enterolobii, and M. javanica using DNA extracted directly from individual galls.

Meloidogyne incognita, M. enterolobii, and M. javanica are the most widespread species of root-knot nematodes in South China, affecting many economically important crops, ornamental plants, and fruit trees. In this study, one pair of Meloidogyne universal primers was designed and three pairs of species-specific primers were employed successfully to rapidly detect and identify M. incognita, M. enterolobii, and M. javanica by multiplex polymerase chain reaction (PCR) using DNA extracted from individual galls. Multiplex PCR from all M. incognita, M. enterolobii, and M. javanica isolates generated two fragments of ≈500 and 1,000, 500 and 200, and 500 and 700 bp, respectively. The 500-bp fragment is the internal positive control fragment of rDNA 28S D2/D3 resulting from the use of the universal primers. Other Meloidogyne spp. included in this study generated only one fragment of ≈500 bp in size. Using this approach, M. incognita, M. enterolobii, and M. javanica were identified and detected using DNA extracted directly from individual galls containing the Meloidogyne spp. at various stages of their life cycle. Moreover, the percentage of positive PCR amplification increased with nematode development and detection was usually easy after the late stage of the second-stage juvenile. The protocol was applied to galls from naturally infested roots and the results were found to be fast, sensitive, robust, and accurate. This present study is the first to provide a definitive diagnostic tool for M. incognita, M. enterolobii, and M. javanica using DNA extracted directly from individual galls using a one-step multiplex PCR technique.

First Report of Meloidogyne enterolobii on Arrowroot in China.

The rhizome of arrowroot (Maranta arundinacea L.) is used as a source of edible starch in many tropical/subtropical areas. In July 2009, cultivated arrowroot plants in a field in Haikou, Hainan Province, China were observed to be exhibiting symptoms of decline, including stunting and yellowing. Roots of affected plants were found to have severe root galling similar to that caused by root-knot nematodes. Meloidogyne sp. females were dissected from the galls. Morphological characteristics of the females fit the description of M. enterolobii Yang & Eisenback (4). The perineal patterns were variable, with moderately high to high dorsal arch and mostly lacking lateral lines, but when present, the lines were not conspicuous, similar to those in the original description.(4). For further confirmation of species identity, isoenzyme patterns of malate dehydrogenase (Mdh) and esterase (Est) phenotypes were analyzed and partial sequences of mtDNA were obtained. Enzyme electrophoresis showed that the phenotypes of Mdh and Est were N1a and VS1-S1 respectively, which were consistent with those of M. enterolobii (1). Amplification and sequencing of the mtDNA between COII and the lRNA gene was accomplished with primers C2F3 (5'-GGTCAATGTTCAGAAATTTGTGG-3') and 1108 (5'-TACCTTTGACCAATCACGCT-3') (2). A DNA fragment of 705 bp was obtained and the sequence (GenBank Accession No. GQ870255) was compared with those in GenBank. A BLAST search indicated the sequence was 100% identical to the sequences of M. mayaguensis (GenBank Accession Nos. AY446969 and AY446970), a synonym of M. enterolobii (3). On the basis of these results, the root-knot nematodes isolated from arrowroot in Hainan were confirmed as M. enterolobii. This species has a high reproduction rate and a wide host range; moreover, it can induce severe galling and is able to overcome the resistance gene Mi-1 in tomato and pepper (4). M. enterolobii has become increasingly important because it has been found in many countries on diverse hosts. In China in recent years, the nematode has been reported on approximately 20 plant species belonging to five families, including Fabaceae, Cucurbitaceae, Solanaceae, Myrtaceae, and Annonaceae. To our knowledge, this is the first record of M. enterolobii parasitizing a plant (i.e., arrowroot) in the family Marantaceae in China. References: (1) P. R. Esbenshade and A. C. Triantaphyllou. J. Nematol. 17:6, 1985. (2) T. O. Powers and T. S. Harris. J. Nematol. 25:1, 1993. (3) J. Xu et al. Eur. J. Plant Pathol. 110:309, 2004. (4) B. Yang and J. D. Eisenback. J. Nematol. 15:381, 1983.

Identification of protease m1 zinc metalloprotease conferring resistance to deltamethrin by characterization of an AFLP marker in Culex pipiens pallens.

BACKGROUND: Continuous and excessive application of deltamethrin (DM) has resulted in the rapid development of insecticide resistance in Culex pipiens pallens. The quantitative trait loci (QTL) responsible for resistance to DM had previously been detected in Cx. pipiens pallens. But locating the QTLs on the chromosomes remained difficult. An available approach is to first characterize DNA molecular markers linked with the phenotype, and then identify candidate genes. METHODS: In this study, the amplified fragment length polymorphism (AFLP) marker L3A8.177 associated with the QTL, was characterized. We searched for potential candidate genes in the flank region of L3A8.177 in the genome sequence of the closely related Cx. pipiens quinquefasciatus and conducted mRNA expression analysis of the candidate gene via quantitative real-time PCR. Then the relationship between DM resistance and the candidate gene was identified using RNAi and American CDC Bottle Bioassay in vivo. We also cloned the ORF sequences of the candidate gene from both susceptible and resistant mosquitoes. RESULTS: The genes CYP6CP1 and protease m1 zinc metalloprotease were in the flank region of L3A8.177 and had significantly different expression levels between susceptible and resistant strains. Protease m1 zinc metalloprotease was significantly up-regulated in the susceptible strains compared with the resistant and remained over-expressed in the susceptible field-collected strains. For deduced amino acid sequences of protease m1 zinc metalloprotease, there was no difference between susceptible and resistant mosquitoes. Knockdown of protease m1 zinc metalloprotease not only decreased the sensitivity of mosquitoes to DM in the susceptible strain but also increased the expression of CYP6CP1, suggesting the role of protease m1 zinc metalloprotease in resistance may be involved in the regulation of the P450 gene expression. CONCLUSION: Our study represents an example of candidate genes derived from the AFLP marker associated with the QTL and provides the first evidence that protease m1 zinc metalloprotease may play a role in the regulation of DM resistance in Cx. pipiens pallens.

Alcohol consumption patterns in the department of Calvados (France).

The individual consumption of alcoholic beverages was determined by interviewing 1.976 people, a representative sample of the population. 92% of males and 74% of females drink alcohol but no more than 4% of females consume over 40 g per day, against 39% males. The average intake is greater in rural than in urban areas. Wine is the most popular beverage but the consumption of cider remains important in rural areas. Apple brandy is also consumed in sizeable quantities by rural males. There are few beer drinkers, except in the younger age groups. The implications of these results are discussed. They probably reflect changes in drinking patterns over time; the traditional locally produced cider and apple brandy are progressively abandoned by the young, who turn to beer and aperitifs. Consequent changes in alcohol related pathology are expected.

[Ionic mechanism of noradrenaline-induced membrane potential changes of neurones in toad dorsal root ganglion].

The membrane conductance and reversal potential were determined for neurones in toad dorsal root ganglion (DRG) with intracellular recording technique during depolarization or hyperpolarization induced by noradrenaline (NA). The effects of blocking agents for potassium or calcium channels on NA-induced membrane potential responses were examined. In 15 neurones, the NA-induced depolarization was accompanied by a 32.6% decrease of membrane conductance; in other 4 neurones, the depolarization was accompanied by an initial increase and subsequent decrease in membrane conductance. The NA hyperpolarization was associated with an increase of membrane conductance by 16.2% (n = 8). The mean reversal potential of NA-induced depolarization was -88.5 +/- 0.9 mV (means +/- SE, n = 4). The NA-induced hyperpolarization was nullified at -89 to -92 mV of membrane potentials (n = 3). Tetraethylammonium superfusion enhanced NA depolarization amplitude by 73.7 +/- 11.9% (means +/- SE, n = 7) and depressed NA hyperpolarization amplitude by 40.5% (n = 4). Intracellular injection of CsCl increased phenylephrine-induced depolarization by 34.5% (n = 4). MnCl2 superfusion decreased the amplitudes of NA-induced depolarization by 50.5 +/- 9.9% (means +/- SE, n = 10), and of NA-induced hyperpolarization by 89.5 +/- 4.9% (means +/- SE, n = 7) respectively. The results suggest that the depolarization or hyperpolarization induced by NA might be mediated by the alteration in activation of K+ or Ca2+ channels.

[Opioid receptor mediated modulation of intrahippocampal enkephalin induced cellular immune function].

In the present work, the effect of intrahippocampal microinjection of opioid receptor antagonist naloxone on the enhancement of cellular immune responses induced by enkephalin was studied in rat. The results showed that (1) the proliferation activity of splenic lymphocytes stimulated by Con A and natural killer (NK) cell activity were decreased with microinjection of 1 microl lipopolysaccharide (LPS,50 ng/microl) into bilateral hippocampus; (2) the decrease of cellular immune responses induced by LPS could be inhibited by a preceding intrahippocampal injection of 1 microl met-enkephalin (10 microg/1 microl); (3) the enhancement of cellular immune responses induced by met-enkephalin could be blocked by an opioid receptor antagonist naloxon (10 microg/microl); and (4) cellular immune responses were also inhibited when naloxon was injected intrahippocampally alone. The above results suggest that the enhancement of cellular immune responses induced by enkephalin was mediated by opioid receptors in hippocampus.

[Improvement of memory function of fornix-fimbria transected rats by transplantation of the superior cervical ganglion into hippocampus].

Memory impairments of passive avoidance response were observed in 38 Wistar rats with bilateral fornix-fimbria transection. After fornix-fimbria lesions the degree of performance decreased from 65.3% to 13.6% (P < 0.01). Autotransplantation of superior cervical ganglion (SCG) into bilateral dorsal hippocampi improved memory function to a considerable extent. In the end of the behavioral experiments, implanted rats were sacrificed for histofluorescence study of grafts and measurement of norepinephrine (NA) content in the hippocampus. These experiments showed that the hippocampal NA content in implanted rats was considerably higher than that in untransplanted fornix-fimbria transected rats and consequently suggested that improvement of memory function was to some extent due to supplement of monoamine transmitter by the transplanted SCG.

[Effect of intrahippocampal microinjection of enkephalin on cellular immune function and brain IL-1 alpha gene expression in rat].

The effect of intrahippocampal microinjection of enkephalin on cellular immune function and hippocampal IL-1 alpha gene expression was studied in rats. The results showed that: (1) The proliferation activity of splenic lymphocytes stimulated by Con A was significantly increased with microinjection of Leu-enkephalin 1 microliter (18 mmol/L) or Met-enkephalin 1 microliter (18 mmol/L) into bilateral hippocampus, but was inhibited by Lipopolysaccharide 1 microliter (50 ng/microliter). The proliferative response of splenic lymphocytes to Leu-enkephalin still persisted after bilateral adrenalectomy. Low doses of Leu- or Met-enkephalin (10(-10), 10(-11) mol/L) were also capable of causing proliferative activity of the Con A- stimulated cultured splenic lymphocytes in vitro. (2) Using RT-PCR technique, IL-1 alpha gene expression was detected in hippocampus 90 min after bilateral intrahippocampal injection of LPS. The LPS-induced IL-1 alpha gene expression in hippocampus could no longer be detected 30 min after microinjection of Met- or Leu-enkephalin into hippocampus. The above results suggested that intrahippocampal enkephalin might play an important role in neuro-immunomodulation by enhancing the inhibition of IL-1 alpha gene expression in hippocampal formation.

Sexing bovine embryos using PCR amplification of bovine SRY sequence.

This study analyses the bovine SRY DNA sequence by direct sequencing procedure, followed by the designation of the PCR primers specific for bovine SRY. Using PCR amplification of bovine SRY gene, the embryo sex was determined. The results of the embryo sex identification were confirmed after the embryo transfer and pregnancies.

[The effects of small dosage inactivated BCG vaccine on cellular immune function of pulmonary chronic obstructive disease patients with deficiency of lung-qi].

UNLABELLED: To investigate the effects of the small dosage inactivated BCG vaccine on the cellular immune function of the patients suffered from pulmonary chronic obstructive disease with deficiency of the Lung-Qi, the authors observed the patients' immune function before and after BCG treatment for half a year. RESULTS: The peripheral blood T lymphocytes subsefs (CD3, CD4, CD8, CD4/CD8) and the conversion ratio of lymphocyte of the patients both were significantly lower than those of the healthy people (P < 0.01). But after the treatment of the small dosage inactivated BCG vaccine for half a year, these parameters of the patients were improved (P < 0.01 or P < 0.05). It indicated that the small dosage inactivated BCG vaccine could improve the damaged cellular immune function.

An unusual case of neonatal peritoneal calcifications associated with hydrometrocolpos.

Neonatal peritoneal calcifications usually suggest a diagnosis of meconium peritonitis, but in this case, a premature baby girl, peritoneal calcifications were caused by hydrometrocolpos secondary to imperforate hymen, a rare association. The patient presented with respiratory distress and ascites and demonstrated abdominal calcifications on plain film. Other radiographic work-up revealed hydrometrocolpos without evidence of gastrointestinal tract obstruction. The patient was diagnosed and treated for imperforate hymen; she was recovered fully.

[Effect of LH-FSH releasing hormone on the sensitivity of cholinergic and adrenergic receptors in toad spinal ganglion neurons].

Intracellular recordings were performed on 81 neurons from 53 isolated toad spinal ganglia (SG). The effects of LH-FSH releasing hormone on the sensitivities of muscarinic receptors and alpha-adrenoceptors located on the soma of SG neurons were observed. Perfusing SG with atropine 10 mumol.L-1 in Ringer's solution depressed the amplitude of depolarization response induced by acetylcholine (ACh, 10-100 mumol.L-1). The depolarization and hyperpolarization induced by norepinephrine (NE, 10-100 mumol.L-1) were blocked by alpha 1-adrenoceptor antagonist prazosin and alpha 2-adrenoceptor antagonist yohimbine respectively. These results indicated that ACh-induced depolarization was mediated by muscarinic receptors while NE-induced depolarization and hyperpolarization were mediated by alpha 1- and alpha 2-adrenoceptors respectively. On the other hand, perfusing SG with LH-FSH releasing hormone 10 mumol.L-1 in Ringer's solution increased the depolarization response caused by ACh or NE, but attenuated NE-caused hyperpolarization response. The above results suggest that LH-FSH releasing hormone may modulate the sensitivities of muscarinic receptors and alpha-adrenoceptors on the soma membrane of toad SG neurons.

Indoor air pollution and lung cancer in Guangzhou, People's Republic of China.

A case-control study comprising 224 male and 92 female incident lung cancer cases and the same number of individually matched hospital controls was conducted from June 1983 to June 1984 in Guangzhou, People's Republic of China, to evaluate the association between indoor air pollution and lung cancer risk. Guangzhou residents were exposed to several sources of pollution in their homes, most importantly to cooking fumes. Increased risks were found among subjects living in a house without a separate kitchen (the exposure odds ratio was 2.4 (95% confidence interval (CI) 1.4-4.2) for men and 5.9 (95% CI 2.1-16.0) for women). Similarly, living in a house with poor air circulation was associated with an exposure odds ratio of 2.1 (95% CI 1.2-3.8) for men and 3.6 (95% CI 1.4-9.3) for women. A trend in the association between lung cancer risk and factors pertaining to house and kitchen ventilation was observed, and a decreasing risk of lung cancer was observed for several variables indicating better ventilation, even after adjustment for potential confounders such as education, occupation, living area, smoking, and history of chronic respiratory diseases. No statistically significant differences were found between cases and controls for frequency of cooking at home, presence of a chimney in the kitchen, or type of cooking fuel. Smoking was clearly related to risk of lung cancer in both men and women, and among nonsmoking women, exposure to tobacco smoke from their spouses was also associated with an increased risk. These results suggest that, in addition to smoking, indoor air pollution may be a risk factor for lung cancer.