[En1 promotes cell proliferation and migration via Hedgehog signaling pathway in esophageal squamous cell carcinoma].

Objective: To explore the function and mechanism of transcription factor En1 in esophageal squamous cell carcinoma (ESCC). Methods: The correlations of En1 with prognosis were analyzed using the overall survival data of 9 397 pan-cancer patients and progression-free survival data of 4 349 pan-cancer patients from The Cancer Genome Atlas (TCGA) database. The En1 expression data in 53 and 155 cases of ESCC and their paired adjacent tissues were from Gene Expression Omnibus (GEO) database and National Genomics Data Center-Genome Sequence Archive(NGDC-GSA)database. Lentivirus was used to generate En1 stable knockout cell lines KYSE180 and KYSE450. The proliferation ability of the cells was detected by cell counting kit 8 and clone formation assay. The migration ability of the cells was detected by Transwell assay. The effect of En1 on the proliferation of ESCC was detected by xenograft experiment in BALB/c-nu/nu mice. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of En1, glioma-associated oncogene family zinc finger 1 (GLI1), glioma-associated oncogene family zinc finger 2 (GLI2) and smoothened (SMO). Results: Pan-cancer data from TCGA showed that patients with low En1 expression had longer overall survival and progression-free survival than patients with high En1 expression (P< 0.001). Data from GEO and GSA databases also showed a high expression level of En1 in ESCC tissues compared with paired tissues (P＜0.001). Proliferation was inhibited after knockout of En1 in KYSE180 and KYSE450 cells (P＜0.001). The colony formation numbers decreased. The colony formation numbers of KYSE180 cells in the shEn1#1 group and the shEn1#2 group were 138.33±23.07 and 127.00±19.70, respectively, significantly lower than that of the shNC group 340.67±12.06 (P<0.001). The colony formation numbers of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were 65.33±2.52 and 9.00±3.00, respectively, significantly lower than that of the shNC group 139.00±13.00 (P<0.001). The migration numbers was inhibited after knockout of En1 [the Transwell numbers of KYSE180 cells in the shEn1#1 group and the shEn1#2 group were 66.67±12.66 and 71.33±11.02, respectively, significantly lower than that of the shNC group 334.67±16.56 (P<0.001). The Transwell numbers of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were 112.33±14.57 and 54.33±5.51, respectively, significantly lower than that of the shNC group 253.33±21.03 (P<0.001)]. Xenograft model showed a slower growth rate of shEn1#1 and shEn1#2 cell lines (P＜0.001). The tumor weights of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were (0.046±0.026)g and (0.047±0.025)g, respectively, significantly lower than that of the shNC group (0.130±0.038)g (P＜0.001). After knockdown of En1, the relative expression levels of GLI1 in KYSE180 cells of the shEn1#1 group and the shEn1#2 group were 0.326±0.162 and 0.322±0.133, and the relative expression levels of GLI1 in KYSE450 cells of the shEn1#1 and shEn1#2 groups were 0.131±0.006 and 0.352±0.050, respectively, which were all lower than that in the shNC group (P＜0.01). After knockdown of En1, overexpression of GLI1 attenuated the inhibitory effect of knockdown of En1 on cell proliferation (P＜0.001), colony formation[the colony formation numbers of the shEn1#1-GLI1 group were 151.00±9.54, higher than 102.33±10.02 (P=0.004) of the shEn1#1-vector group] and migration [the migration numbers of the shEn1#1-GLI1 group were 193.67±10.07, higher than 109.33±11.50 (P<0.001) in the shEn1#1-vector group]. In clinical samples of ESCC, major regulatory factors of the Hedgehog pathway were up-regulated and the pathway was activated. Conclusion: En1 promotes the proliferation and migration of ESCC cells by regulating the Hedgehog pathway and can be used as a new potential target for targeted therapy of ESCC.

A comprehensive analysis of nucleotide excision repair characteristics defines a novel prognostic signature for acute myeloid leukemia.

OBJECTIVE: Nucleotide excision repair (NER) has been associated with various types of malignant tumors. However, the precise roles of nucleotide excision repair-related genes (NERGs) in acute myeloid leukemia (AML) remain incompletely understood. Hence, this study aimed to develop a prognostic signature incorporating NERGs in AML, which could potentially predict patient outcomes. MATERIALS AND METHODS: By querying the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases, we acquired RNA-seq data and clinical information pertaining to AML. To identify differentially expressed NERGs (DE-NERGs), we employed the Wilcoxon rank-sum test. Based on the expression patterns of DE-NERGs with prognostic significance, patients were categorized into two subgroups. A prognostic signature was developed through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to compare the differentially expressed genes (DEGs) between these two groups. Additionally, a nomogram was constructed using multivariate analysis. The biological pathways involved were elucidated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA). RESULTS: We developed a prognostic model based on an 11-gene signature. Furthermore, the risk score derived from this model was demonstrated to independently serve as a prognostic marker for patients diagnosed with AML. CONCLUSIONS: Our prognostic model, based on NERGs, was developed and validated to provide insights into the onset and progression of AML and establish a foundation for more effective treatment. Our findings not only contribute to clinical decision-making but also underscore the significance of nucleotide excision repair. Furthermore, they may pave the way for the development of targeted therapeutic strategies specifically focused on this process.

[Clinical significance of intersphincteric resection related anatomy effect on surgical safety].

The anatomical studies of intersphincteric resection (ISR) have made remarkable progress in recent years. The anatomy of internal, external sphincter and hiatal ligament has been further understood. In this paper, the generation and functional mechanism of ISR related anatomy are described from the embryonic development process, and then the influence of hiatal ligament and internal sphincter on ISR surgery is analyzed respectively according to the anatomical characteristics. Finally, the correlation analysis of anatomical factors on the common problems of mucosal bleeding and instrument anastomosis in ISR is carried out. The objective of this paper is to improve the safety of ISR surgery by providing detailed anatomical explanations.

[Application of cochlear nerve action potential monitoring in the resection of vestibular schwannomas].

Objective: To investigate the application of cochlear nerve action potential (CNAP) monitoring in the resection of vestibular schwannoma, especially evaluating its significance for hearing preservation. Methods: From April 2018 to December 2021, 54 patients with vestibular schwannoma who underwent resection via retrosigmoid approach were collected in Chinese PLA General Hospital. Before surgery, all patients had effective hearing (AAO-HNS grade C or above). Brainstem auditory evoked potential (BAEP) combined with CNAP monitoring was performed during surgery. The CNAP monitoring was combined with continuous monitoring and cochlear nerve mapping. And patients were divided into hearing preservation group and non-preserved group according to postoperative AAO-HNS grade. SPSS 23.0 software was used to analyze the differences of CNAP and BEAP parameters between the two groups. Results: A total of 54 patients completed intraoperative monitoring and data collection, including 25 males (46.3%) and 29 females (53.7%), aged 27-71 years with an average age of 46.2 years. The maximum tumor diameter were (18.1±5.9) mm (range 10-34 mm). All tumors were totally removed with preserved facial nerve function (House-Brackmann grade I-II). The hearing preservation rate of 54 patients was 51.9% (28/54). During surgery, the V wave extraction rate of BAEP waveform was 85.2% (46/54) before tumor resection, 71.4% (20/28) in the hearing preservation group after tumor resection, and disappeared in the hearing preservation group (0/26). CNAP waveform was elicited in 54 patients during operation. Differences were found in the distribution of CNAP waveforms after tumor resection. The waveforms of the hearing-preserving group were triphasic and biphasic, while those in the non-preserving group were low-level and positive. For hearing preservation group, the amplitude of N1 wave after tumor resection was significantly higher than that before tumor resection[14.45(7.54, 33.85)µV vs 9.13(4.88, 23.35)µV, P=0.022]; However, for the non-preserved group, the amplitude of N1 wave after tumor resection was significantly lower than that before tumor resection [3.07(1.96, 4.60)µV vs 6.55(4.54, 9.71)µV, P=0.007]; After tumor resection, the amplitude was significantly higher than that of the unreserved group [14.45(7.54, 33.85)µV vs 3.07(1.96, 4.60)µV, P<0.001]. Conclusions: BAEP combined with CNAP monitoring is conducive to intraoperative hearing protection, and the application of cochlear nerve mapping can prompt the surgeon to avoid nerve injury. The waveform and N1 amplitude of CNAP after tumor resection have a certain value in predicting postoperative hearing preservation status.

[Intraoperative cochlear nerve monitoring in microvascular decompression of hemifacial spasm and resection of vestibular schwannoma].

Objective: To analyze the application of direct cochlear nerve monitoring technology-cochlear nerve action potential (CNAP) monitoring in resection of vestibular schwannoma (VS) and to compare with which in microvascular decompression (MVD) of hemifacial spasm (HFS), in order to provide reference for identification of the cochlear nerve during VS resection surgery and predicting postoperative hearing preservation. Methods: From June 2018 to March 2022, patients with facial spasm and vestibular schwannoma who underwent retrosigmoid approach surgery at the Chinese PLA General Hospital were collected. Before surgery, there were a total of 11 HFS patients and 30 VS patients. Before surgery, the former had hearing level of class A(AAO-HNS), while the latter had serviceable hearing (AAO-HNS class A-B), with a maximum tumor diameter of≤20 mm. CNAP combined with Auditory Brainstem Response (ABR) monitoring was performed during surgery. SPSS 23.0 software was used to analyze the differences of ABR and CNAP parameters between the two groups. Results: The preoperative ABR test in the VS group showed that the latency of wave V and I-V interval were significantly prolonged compared to the HFS group (t=8.36, P<0.001; t=4.61, P<0.001).In VS group, all tumors were totally removed with preserved facial nerve function (House-Brackmann grade Ⅰ-Ⅱ). The serviceable hearing preservation rate was 63.3%. In the HFS group, the initial CNAP waveforms were triphasic and biphasic, with N1 wave latency of (4.32±0.37) ms and amplitude of 25.20 [15.63, 35.40]µV. The distribution of CNAP waveforms before tumor resection in the VS group was the same as that in the HFS group, and which in the hearing preservation group after surgery was also the same. Compared with the HFS group, the latency of N1 wave was prolonged (t=2.670, P=0.011;t=4.584, P<0.001), and the amplitude of N1 wavein the VS group before tumor resection was lower (Z=-3.001, P=0.003). The amplitude of N1 wave in the hearing preservation group after surgery was 20.20 [6.23, 40.90] µV,which was significantly higher than that before tumor resection (Z=-2.133, P=0.033), but there was no statistically significant difference compared to the HFS group (Z=-0.495, P=0.621). Conclusions: The reference range of CNAP in normal hearing population can be preliminarily obtained by the analysis of CNAP in MVD surgery. The latency of N1 wave in VS patients is prolonged and the amplitude of N1 wave is decreased due to tumor compression. The CNAP waveform combined with the change of N1 wave amplitude can provide reference for intraoperative mapping of the cochlear nerve and prediction of postoperative hearing preservation.

[Treatment and prognosis of primary ocular adnexal extranodal marginal zone mucosa-associated lymphoid tissue lymphoma: a report from a single center].

Objective: This study aimed to see how different initial treatment regimens affected the long-term prognosis of patients with extranodal marginal zone mucosa-associated lymphoid tissue lymphoma confining to the ocular adnexal (OAML) . Methods: Between April 2008 and April 2019, 109 patients with initial mucosa-associated lymphoid tissue confining to ocular adnexal were evaluated and followed-up, and the prognosis of various initial treatment regimens were examined. Results: A total of 36 patients underwent complete surgical resection of the lesions, and 73 patients had residual lesions after surgery, of which 37 patients chose watchful waiting, and 36 patients chose treatment. The treatment regimen included local radiotherapy and systemic treatment (chemotherapy, immunochemotherapy, the combination of radiotherapy and chemotherapy, etc.) , and no serious toxic and side effects were observed in patients receiving systemic treatment. The median follow-up time was 61 (10-142) months. The 5-year and 10-year progression-free survival (PFS) of monocular involvement patients were 78.2% and 76.0% . The 5-year and 10-year PFS rates of patients with binocular involvement were 64.4% and 23.5%. There was significant diference in PFS between patients with monocular and binocular involvement (P=0.010) . Patients who received additional treatment had higher PFS than those patients in the watchful waiting group (P=0.046) . The 5-year PFS was 71.4% and 90.1% among patients in the watchful waiting group and those who received additional treatment, whereas the 10-year PFS was 63.5% and 75.1% , respectively. Patients with OAML were still a risk of disease progression after 5 years. Conclusions: Patients with binocular involvement OAML at the start of the disease had a poor prognosis, but treatment could reduce the risk of recurrence/progression. Systemic therapy is one of the first-line treatment options for patients with OAML, who require long-term monitoring.

Reduced blood circulating calcium level is an outstanding biomarker for preeclampsia among 48 types of human diseases.

BACKGROUND: Calcium ion (Ca2+) is essential for human physiology by regulating various signal transduction pathways inside all cells and in the blood circulation. AIM: We compared circulating Ca2+ levels in the healthy control against 48 different types of human diseases. DESIGN: A total of 144 201 independent test results of Ca2+ levels from 48 clinically defined diseases and 141 679 independent test results of Ca2+ from healthy individuals who came to the hospital for annual physical examination were retrieved during the past 5 years. METHODS: Ca2+ was determined by the standard 'Arsenazo III method' in the clinical laboratory of Affiliated Hospital of Qingdao University. We analyzed all data using RStudio V.1.3.1073 and python libraries 3.8. RESULTS: All 48 types of diseases had decreased Ca2+ levels than the healthy control based on either mean or median values. Patients suffering from preeclampsia had the lowest Ca2+ levels among all 48 diseases. The perfect area under the curve, sensitivity, and specificity values of 1.0, 0.96 and 0.96 indicated that Ca2+ was an excellent biomarker for diagnosing preeclampsia. Extremely low Ca2+ was present in patients suffering kidney-related diseases. Since the correlation between each disease on the statistical features is proportional to their vector distance, the two-component analysis revealed that preeclampsia, sepsis and chronic obstructive pulmonary disease were closely related among 48 diseases. CONCLUSIONS: All human diseases were associated with reduced circulating Ca2+ levels, where the decreased Ca2+ was a perfect biomarker for preeclampsia. Kidney-related conditions were related to over-down-regulation of Ca2+ levels. The resemblance of preeclampsia to sepsis and chronic obstructive pulmonary disease based on two-component analysis suggested that the three unrelated diseases might share a similar mechanism of the circulating Ca2+ regulation.

[Recognition of surgical anatomy for intersphincteric resection].

Intersphincteric resection (ISR) involves the anatomy of hiatal ligament, internal and external sphincter and conjoined longitudinal muscle. The hiatal ligament is actually a branch of the longitudinal muscle of rectum, shown as an uneven ring attached to the levator ani muscle. The internal sphincter is the end of the circular muscle of rectum which begins at the level of hiatal ligament formation. The distance from the upper boundary of internal sphincter to dentate line is significantly different among individuals. Although there is adipose tissue in the space between the internal and external sphincters, no evidence of mesentery structure in the anal canal is found as in the rectum. The conjoined longitudinal muscle is the remaining branch of the longitudinal muscle, whose return passes through the external sphincter and ends at the anococcygeal ligament/coccyx after reaching the anal margin. The synergistic action of conjoined longitudinal muscle and the hiatal ligament participates in the defecation process. The individualized difference of ISR-related anatomy affects the operation, especially the anastomosis.

Analysis of the MCL-1 gene in Chinese women with idiopathic premature ovarian insufficiency.

OBJECTIVE: Animal studies have demonstrated that myeloid cell leukemia-1 (Mcl-1) gene deficiency leads to premature ovarian failure and decreased reproductive ability in mice. This study investigated the relationship between MCL-1 gene variation and idiopathic premature ovarian insufficiency (POI) in Chinese women. METHODS: A total of 200 idiopathic POI patients and 100 healthy controls were recruited for this study, and peripheral blood was collected. First, genomic DNA was extracted from peripheral leukocytes. Then, the entire coding region and splice sites of the MCL-1 gene were amplified by polymerase chain reaction. Chi-squared tests were used to compare the genotype distribution and allele frequency of single nucleotide polymorphisms between the POI and control groups. RESULTS: Three mutations of the MCL-1 gene (c.-36C > T, c.-131C > T and c.78C > T) were identified. After data analysis, c.-36C > T and c.-131C > T in the 5'-untranslated region were both found in the POI group and the control group. No difference was found in the genotype distribution or allelic frequency of either variant between the POI group and the control group (p > 0.05). The synonymous variant (c.78C > T) in exon 1 was discovered in only one of the control subjects and did not result in a change in amino acid sequence (p.Gly26Gly). CONCLUSION: MCL-1 gene mutation may not be associated with idiopathic POI in Chinese women.

Morphology is not a reliable taxonomic tool for the genus Lernaea: molecular data and experimental infection reveal that L. cyprinacea and L. cruciata are conspecific.

BACKGROUND: Species belonging to the genus Lernaea are cosmopolitan parasites that can infect many different freshwater fish hosts. Due to a high degree of morphological intraspecific variability and high levels of interspecific similarities, their classification is extremely difficult and controversial. Although the suitability of the shape of cephalic horns has been questioned decades ago by some experimental infection studies, this character still plays the central role in the identification of Lernaea spp. METHODS: We used the nominal species Lernaea cyprinacea and Lernaea cruciata to test the hypothesis that the shape of the anchor can exhibit host-induced morphological variability, and that the two taxa may be synonymous. RESULTS: We examined 517 wild or farmed specimens of five host fish species (four cyprinids and a mosquitofish), and found that all 16 parasite specimens collected from mosquitofish could be morphologically identified as L. cruciata, whereas the remaining 25 parasite specimens were all identified as L. cyprinacea. We experimentally infected goldfish and mosquitofish specimens with offspring (copepodids) of a single L. cyprinacea specimen: the adult parasites from goldfish were morphologically identified as L. cyprinacea, and those from mosquitofish as L. cruciata. We then used molecular data to corroborate that all these specimens are conspecific. CONCLUSIONS: Our results suggest that L. cyprinacea and L. cruciata may be synonyms, misidentified as different species as a result of host-induced morphological variation. Given the current shortage of molecular data for the genus Lernaea, in order to resolve the taxonomy of this genus (determine the exact number of species), future studies should aim to sequence as much molecular data as possible, and conduct further experimental infections.

[Mechanism and anatomy recognition of neurovascular bundle injury from different perspectives of transabdominal and transanal approach].

The neurovascular bundle (NVB) starts at the lateral angle of the seminal vesicle (the initial part), passes posterolateral of the prostate gland (the main part), and ends at the cavernous body of the penis (the cavernous part). In low rectal surgery, different transabdominal and transanal perspectives result in different NVB injury risks. In the perspective of transabdominal operation, the separation between the initial part of NVB and Denonvilliers fascia and the anatomical variation of the two lateral sides of Denonvilliers fascia increases the risk of NVB injury, and conformation separation may take into account the convenience of separationand the protection of NVB. In the perspective of transanal operation, when separating the main part with NVB and mesorectum, the perspective of the transanal, unidirection traction and excessive dissection increase the risk of NVB main exposure. Clear anatomical identification helps the protection of NVB in the transanal operation. At present, the medical evidence on the difference of NVB injury in different perspectives of transabdominal and transanal approach is still in need of relevant clinical researches.

[Anatomic factors and preventive techniques for anastomotic complications after transanal total mesorectal excision].

Whether the transanal total mesorectal resection (taTME) techniques increase the risk of anastomotic failure is inconclusive. This paper discusses the anastomotic problems of taTME from different aspects including anatomical factors and technical characteristics. In terms of the anatomic and physiological characteristics of the lower rectum, the Hiatal ligament and the density of the perirectal space is a disadvantage to the anastomosis of taTME, while the prolapse of the rectum may be a beneficial factor. Due to the unique technical characteristics of taTME, the main reason affecting its anastomosis at present is that the caudal space at the distal end is not sufficiently mobilized, especially for male and lower anastomosis. In addition, stapled anastomosis at the level of anorectal ring may cause more problems, while manual anastomosis at the lower level may bring better results.

[A follow-up study on the clinical characteristics among patients with diabetes mellitus combined with acute myocardial infarction].

Objective: To investigate the clinical characteristics of diabetic patients combined with acute myocardial infarction (AMI) and to compare the prognosis between diabetic and non- diabetic patients in 4-5 years after the onset of AMI. Methods: Followed the certain inclusive and exclusive criteria, a total of 420 patients with acute myocardial infarction were included and divided into diabetes group (group D) and non-diabetes group (group N) with numbers as 161 people and 259 respectively. Baseline data, clinical information, short-term outcome and long-term prognosis of the two groups were compared and analyzed. Results: Among the patients with diabetes, the average age was older (65.65±11.33 vs. 63.30±15.34), with fewer males (64.59% vs. 79.92%); and more likely to have other complications as hypertension (64.60% vs. 53.28%) or hyperlipidemia (42.24% vs. 26.25%). 59.29% of the patients in group D showed pathological changes in 3 major coronary arteries, which were significantly more than its counterpart (40.83%). The proportion of patients that had undergone the coronary artery bypass, grafting (11.11% vs. 5.31%) appeared also higher. There was no significant difference seen in the short-term outcomes between the two groups, but results from the long-term follow-up program showed that both the incidence of Major Adverse Cardiovascular Events (MACE) (50.67% vs. 27.72%) and the all-cause mortality (20.00% vs. 9.90%) in group D were higher than those appeared in group N (27.72%). Conclusions: Patients suffered from the combination of both diabetes and acute myocardial infarction appeared older in age, more in females, with more complications and the coronary artery lesions were more severe and wider. During hospitalization, no significant difference was seen regarding the short-term outcomes between the two groups but the results from long-term follow-up process showing that the risk of MACE events was significantly higher in patients with type2 diabetes.

Zoledronic Acid Improves Bone Quality in the Streptozotocin-Induced Diabetes Rat through Affecting the Expression of the Osteoblast-Regulating Transcription Factors.

AIMS: To evaluate the short term effect of zoledronic acid on bone remodeling in the streptozotocin induced diabetes rats. MATERIALS AND METHODS: Diabetes was induced by an injection of streptozotocin (60 mg/kg). The rats were treated with zoledronic acid (0.1 mg/kg) at the onset of diabetes (Z-I group) and 2 weeks later (Z-II group). Rats were sacrificed at the 1, 2, 3, 4 and 5 weeks after the onset of diabetes. Real-time PCR and western blot were performed to detect the expression of the following osteogenic gene mRNAs and their proteins: bone morphogenetic proteins 2 (BMP2), Runx2, Osterix and Noggin. The bone mineral density (BMD) and the mechanical resistance test was measured. RESULTS: BMP2, Runx2 and Osterix mRNA and protein expression in group D had regulated down, while Noggin expression increased. Z-I treatment could reverse the results. However group Z-II showed only a transient reversing effect. On the 5th week in group D, the BMD decreased, the bone trabecular distance increased, while the trabecular thickness and bone trabecular volume were reduced, the biomechanics index decreased significantly. Zoledronic acid treatment restored these alterations. CONCLUSIONS: Zoledronic acid administered in the early stage of the diabetes could prevent the osteopenia. The underlying mechanisms might be that zoledronic acid treatment reversed the effect of diabetes on the expression of osteoblast-regulating transcription factors: BMP2, Runx2 and Osterix.

Effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells.

This study investigates the effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells. Epithelial ovarian cancer tissues were collected from 60 patients, benign ovarian tissues from 45 patients and normal ovarian tissues from 30 patients. Human epidermal growth factor receptor 2 (HER2) protein expression was measured by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction (RT-PCR). Proliferation and apoptosis of SKOV3 cells were then measured by MTS assay and flow cytometry and cleaved caspase-3 expression was detected by Western blot. Our results established that HER2 protein is expressed in tumor tissues, benign tissues and normal tissues and its positive expression rate in tumor tissues is significantly higher than in benign tissues and normal tissues (p<0.05). In addition, the relative HER2 mRNA expression in epithelial ovarian tumor tissues was 55 times higher than that in normal ovarian tissues (p<0.01). Our research confirmed that trastuzumab significantly inhibited SKOV3 cell proliferation and increased cell apoptosis and cleaved caspase-3 expression in the experimental group compared to controls (p<0.05). In conclusion, HER2 protein is over-expressed in epithelial ovarian cancer tissues, and trastuzumab exerts anti-tumor effect by inhibiting cell proliferation and inducing apoptosis, suggesting it might be a novel approach for the treatment of ovarian cancer.

Basal position of two new complete mitochondrial genomes of parasitic Cymothoida (Crustacea: Isopoda) challenges the monophyly of the suborder and phylogeny of the entire order.

BACKGROUND: Isopoda is a highly diverse order of crustaceans with more than 10,300 species, many of which are parasitic. Taxonomy and phylogeny within the order, especially those of the suborder Cymothoida Wägele, 1989, are still debated. Mitochondrial (mt) genomes are a useful tool for phylogenetic studies, but their availability for isopods is very limited. To explore these phylogenetic controversies on the mt genomic level and study the mt genome evolution in Isopoda, we sequenced mt genomes of two parasitic isopods, Tachaea chinensis Thielemann, 1910 and Ichthyoxenos japonensis Richardson, 1913, belonging to the suborder Cymothoida, and conducted comparative and phylogenetic mt genomic analyses across Isopoda. RESULTS: The complete mt genomes of T. chinensis and I. japonensis were 14,616 bp and 15,440 bp in size, respectively, with the A+T content higher than in other isopods (72.7 and 72.8%, respectively). Both genomes code for 13 protein-coding genes, 21 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and possess a control region (CR). Both are missing a gene from the complete tRNA set: T. chinensis lacks trnS1 and I. japonensis lacks trnI. Both possess unique gene orders among isopods. Within the CR of I. japonensis (284 bp), we identified a repetitive region with four tandem repeats. Phylogenetic analysis based on concatenated nucleotide sequences of 13 protein-coding genes showed that the two parasitic cymothoids clustered together and formed a basal clade within Isopoda. However, another parasitic cymothoid, Gyge ovalis Shiino, 1939, formed a sister group with the suborder Limnoriidea Brandt & Poore in Poore, 2002, whereas two free-living cymothoid species were located in the derived part of the phylogram: Bathynomus sp. formed a sister group with the suborder Sphaeromatidea Wägele, 1989, and Eurydice pulchra Leach, 1815 with a clade including Bathynomus sp., Sphaeromatidea and Valvifera G. O. Sars, 1883. CONCLUSIONS: Our results did not recover the suborders Cymothoida and Oniscidea Latreille, 1802 as monophyletic, with parasitic and free-living cymothoidans forming separate clades. Furthermore, two parasitic cymothoidans formed the sister-clade to all other isopods, separated from Epicaridea Latreille, 1825, which challenges currently prevalent isopod phylogeny. Additional mt genomes of parasitic and free-living isopods might confer a sufficient phylogenetic resolution to enable us to resolve their relationships, and ultimately allow us to better understand the evolutionary history of the entire isopod order.

[Management of toxicities associated with pegaspargase in treatment of patients with lymphoid malignancy: experience from 443 cases in a single center].

Objective: To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience. Methods: Clinical data of patients who received chemotherapy including pegaspargase in the Department of Hematology of Beijing Tongren hospital during August 2011 to December 2015 were retrospective analyzed, and the adverse effects of pegaspargase and the management experience was summarized. Results: A total of 129 patients with 443 times of pegaspargase used during this period. The common adverse reactions included allergic reactions in 2 cases (1.6%), acute pancreatitis in 19 (14.7%) including 6 acute symptomatic pancreatitis and 13 chemical pancreatitis with elevated pancreatin, hypertriglyceridemia in 15 cases(11.6%), hyperglycemia in 85 (65.9%), hypoglycemia in 7 (5.4%), elevated aminotransferase in 25 (19.4%), hyperbilirubinemia in 21 (15.5%), hypoalbuminemia in 62 (48.1%), prolonged APTT in 61 (47.3%), prolonged PT in 22 (17.1%), prolonged TT in 15 (11.6%), hypofibrinogen in 75 (58.1%), thrombus in 11 (8.5%) and bleeding in 3 (2.3%). The above adverse reactions were improved by symptomatic treatment of anti allergy, inhibition of secretion of pancreatic juice, lipid lowering, hypoglycemic, liver preservation, supplementation of plasma and hemostasis, respectively. Some serious adverse reactions affected the application of pegaspargase, even lead to discontinuation of the aspartate. Conclusion: Though adverse effects associated with pegaspargase are extensive, most patients can successfully complete the chemotherapy containing the pegaspargase with close monitoring and timely treatment.

Satb2 ablation decreases PTZ-induced seizure susceptibility and pyramidal neuronal excitability.

Special AT-rich sequence-binding protein 2 (Satb2) is a transcriptional regulator and people with SATB2 mutation or duplication could display epilepsy. However, whether Satb2 is related with epilepsy and its mechanisms are largely unexplored. Here we found that the expression of Satb2 was decreased following the neuronal hyperactivities. Ablation of Satb2 in mice would decrease incidence and stage of seizure induced by intraperitoneal injection of pentylenetetrazol (PTZ). At cellular levels, we found pyramidal neuronal excitability and excitatory synaptic inputs in CA1 were decreased in Satb2 mutant mice. Taking together, we proved that deletion of Satb2 in mice increased PTZ seizure threshold probably by modulating neuronal excitability.

Effects of dietary supplementation with carnosine on meat quality and antioxidant capacity in broiler chickens.

1. This study aimed to investigate the effects of carnosine supplementation on meat quality, antioxidant capacity and lipid peroxidation status in broiler chickens. 2. A total of 256 1-d-old male Arbor Acres broilers were randomly assigned to 4 treatments consisting of 8 replicates of 8 chickens each. The birds were supplied with 4 different diets: a basal diet or a basal diet supplemented with 100, 200 or 400 mg/kg carnosine, respectively. The whole experiment lasted 42 d. 3. The results showed that dietary supplementation with carnosine linearly increased the values of pH45 min and redness and reduced drip loss of breast meat. Dietary carnosine increased the activity of antioxidant enzymes in liver, serum and breast meat and decreased the contents of lipid peroxides at 21 and 42 d of age. 4. These findings indicated that dietary supplementation with carnosine was beneficial to enhance meat quality, antioxidant capacity and decrease lipid peroxidation status of breast meat.