[Preliminary analysis of neuroprotective effects of capillary fascia preservation recurrent laryngeal nerve anatomical method in right level â ¥ dissection].

Objective: To investigate the application and effect of capillary fascia preservation between the recurrent laryngeal nerve (RLN) and common carotid artery (fascia preservation method) in nerve protection when dissecting right level Ⅵ lymph nodes for patients with papillary thyroid carcinoma. Methods: A retrospective cohort study enrolling 195 patients with papillary thyroid carcinoma undergoing right level Ⅵ lymph node dissection in Beijing Tongren Hospital from March 2021 to August 2022 was carried out. The RLN was dissected by fascia preservation method in study group and by routine method in control group. The intraoperative electrical signal amplitude of the RLN, the number of dissected lymph nodes, and the postoperative complications were recorded and analyzed. Results: A total of 195 patients (study group: 94 cases, control group: 101 cases) were collected. There were 71 males and 124 females, with the median age of 32 (39, 51) years. In the study group, the total number of right level Ⅵ lymph nodes was significantly larger than the number of right Ⅵa level lymph nodes [8 (6, 11) vs 6 (4, 8), P<0.001]. There were no significant differences between the two groups in the number of level Ⅵa or level Ⅵb lymph nodes [Ⅵa: 6 (4, 8) vs 5 (3, 7), P=0.373; Ⅵb: 3 (1, 4) vs 2 (1, 4), P=0.337] and metastasis rate [Ⅵa: 51.1% (48/94) vs 52.5% (53/101), P=0.844; Ⅵb: 12.8% (12/94) vs 15.8% (16/101), P=0.541]. The ratio of electromyography (EMG) amplitude R2 in lower level Ⅵ and entry into larynx (grouped as>90%, 50%~90%,<50%) in the study group was significantly higher than that in the control group (P<0.001). No significant differences were detected between the two groups in temporary RLN paralysis [1.1% (1/94) vs 2.0% (2/101), P=1.000]. Conclusions: Fascia preservation method can decrease the stimulus and traction to RLN and preserve the capillary network serving RLN. It can thoroughly dissect lymph nodes and decrease the injury of RLN.

[Clinical characteristics and prognosis in papillary thyroid carcinoma patients with recurrent laryngeal nerve invasion].

Objective: To investigate the clinical characteristics and risk factors of postoperative recurrence in papillary thyroid carcinoma (PTC) patients with recurrent laryngeal nerve (RLN) invasion. Methods: The data of PTC patients with recurrent laryngeal nerve invasion treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed. The acoustic parameters were compared between different subgroups. Kaplan-Meier method was used to calculate the overall survival (OS) and the recurrence-free rate (RFS), and univariate and multivariate Cox regression analyses were performed to determine the risk factors for postoperative recurrence. Results: A total of 150 PTC patients were enrolled in the final analysis, including 102 females and 48 males, with an average age of (53.5±13.7) years, and 62 patients (41.3%) aged over 55 years. There were 88 cases with stage Ⅰ, and 62 cases with stage Ⅲ. Fifty-five patients presented with preoperative vocal cord paralysis. There were 75 cases appearing adhesion between tumor or lymph node and recurrent laryngeal nerve while 75 cases presented with direct invasion. The comparisons of acoustic parameters showed that patients with RLN invasion had higher jitter compared with patients without RLN invasion [2.3% (1.4%, 3.2%) vs 1.8% (0.8%, 2.6%), P<0.001]. Moreover, patients with preoperative vocal cord paralysis (VCP) had higher jitter[3.1% (2.2%, 4.6%) vs 2.0% (1.1%, 2.8%), P<0.001] and shimmer [7.1% (4.9%, 9.9%) vs 5.5% (4.2%, 7.3%), P<0.001] and shorter maximum phonation time (MPT) [8.0 (6.0, 10.0) s vs 12.0 (10.0, 15.3) s, P<0.001] compared with patients without preoperative VCP. However, there was no statistical difference in acoustic parameters between cases with RLN adhesion and RLN invasion (all P>0.05). Postoperative follow-up time ranged between 12-196 months, with an average of (65.0±35.9) months. Sixteen patients (10.7%) had recurrence or metastasis, and 8 cases (5.3%) died of recurrence or metastasis. The 5-year OS rate was 95.1%, and the 10-year OS rate was 92.8%. The 5-year RFS rate was 88.9%, and the 10-year RFS rate was 86.2%. Univariate Cox analysis showed that age of onset ≥ 55 years, preoperative recurrent laryngeal nerve palsy, laryngeal, trachea or esophageal invasion were the risk factors for postoperative recurrence of PTC with RLN invasion (all P<0.05). Multivariate Cox analysis showed that age of onset ≥ 55 years (OR=1.060, 95%CI: 1.011-1.110, P=0.015) was an independent risk factor. Conclusions: Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in PTC patients with RLN invasion. Preoperative acoustic parameters may provide reference for evaluation of RLN function.

[A new classification of maxillary defect and simultaneous accurate reconstruction].

Objective: To select the preferred flaps for the reconstruction of different maxillary defects and to propose a new classification of maxillary defects. Methods: A total of 219 patients (136 males and 83 females) underwent the simultaneous reconstruction of maxillary defects in the Beijing Tongren Hospital, Capital Medical University, between January 2005 and December 2018 were reviewed. Age ranged from 16 to 78 years. Based on the proposed new classification of the maxillary defects, 22 patients with class Ⅰ defects (inferior maxillectomy), 44 patients with class Ⅱ defects (supperior maxillectomy), 132 patients with class Ⅲ defects (total maxillectomy) and 21 patients with class Ⅳ defects (extensive maxillectomy) were enrolled. Survival rate, functional and aesthetic outcomes of flaps were evaluated. Survival analysis was performed in 169 patients with malignant tumor, Kaplan-Meier method was used to calculate the survival rate, and Log-rank method was used to compare the difference of survival rate in each group. Results: A total of 234 repairs for maxillary defects were performed in 219 patients. Fibula flaps were used in 4/13 of class Ⅰ defects; temporal muscle flaps (11/24, 45.8%) and anterolateral thigh flaps (6/24, 25.0%) used in class Ⅱ defects; temporal muscle flaps (71/128, 55.5%), anterolateral thigh flaps (6/24, 25.0%) and fibula flaps (12/128, 9.4%) used in class Ⅲ defects; and anterolateral thigh flaps (8/20, 40.0%) and rectus abdominis flaps (8/20, 40.0%) used in class Ⅳ defects. The success rate of local pedicled flaps was 95.6% (109/114) and that of free flaps was 95.8% (115/120). Thrombosis(10/234,4.3%) was a main reason for repair failure. Among the followed-up 88 patients, swallowing and speech functions recovered, 82 (93.2%) of them were satisfied with appearance, and 75 (85.2%) were satisfied with visual field. The 3-year and 5-year overall survival rates were 66.5% and 63.6%, and the 3-year and 5-year disease-free survival rates were 57.1% and 46.2%, respectively, in the 169 patients with malignant tumors. Conclusion: A new classification of maxillary defects is proposed, on which suitable flaps are selected to offer patients good functional and aesthetic outcomes and high quality of life.

[Clinical comparative study of free posterior tibial artery perforator flap and radial forearm free flap for head and neck reconstruction].

Objective: To compare the clinical application results of the FPTF (free posterior tibial artery perforator flap) and RFFF (radial forearm free flap) for reconstruction of head and neck defects. Methods: A retrospective analysis of 27 cases treated with FPTF (19 males and 8 females, aged 14-69 years) and 24 cases with RFFF (11 males and 13 females, aged 22-69 years) for head and neck defect reconstruction at Beijing Tongren Hospital of Capital Medical University from January 2015 to December 2020 was conducted. Flap size, vascular pedicle length, matching degree of recipient area blood vessels, preparation time, total operation time, hospital stay, recipient area complications, donor area complications and scale-based patient satisfaction were compared between two groups of patients with FTPF and RFFF. SPSS 26.0 statistical software was used for statistical analysis. Results: There was no statistically significant difference between the two groups of patients in tumor T staging (P=0.38), primary sites (P=0.05) and mean flap areas ((53.67±29.84) cm2 vs. (41.13±11.08) cm2, t=-1.472, P=0.14). However the mean vascular pedicle length of FPTF was more than that of RFFF ((11.15±2.48)cm vs. (8.50±1.69)cm, t=-4.071, P<0.01). The donor sites of 4 patients in FPTF group could be sutured directly, while all the 24 patients in RFFF group received skin grafts from the donor sites. There was no statistically significant difference in the recipient area arteries between two groups of flaps (P=0.10), with more commonly using of the facial artery (RFFF: FPTF=21∶27), but there was significant difference in the recipient area veins (P<0.01), with more commonly using of the external jugular vein in RFFF (14/24) than FPTF (4/32) and the posterior facial vein in FPTF (27/32) than RFFF (9/24). There were 10 recipient complications and 3 donor complications in RFFF group; no recipient complication and 3 donor complications occurred in FPTF group. With patient's subjective evaluation of the donor site at 12 months after surgery, FPTF was better than RFFF (χ²=22.241, P<0.01). Conclusions: FPTF is an alternative to RFFF in head and neck reconstruction and has unique advantages in aesthetics and clinical application.

[Application of submental artery perforator flap in reconstruction surgery in pharyngeal carcinoma].

Objective: To evaluate clinical applications and efficacy of submental artery perforator flap in reconstruction surgery after removal of pharyngeal carcinoma. Methods: A total of 27 patients in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University were included, 23 males and 4 females with age from 40 to 70 years old, and 17 patients were hypopharyngeal carcinoma (HPC) and 10 patients were oropharyngeal carcinoma (OPC). All patients underwent tumor resection followed by simultaneously reconstruction surgery using submental artery perforator flap between January 2015 and December 2019. Of 5 patients with palatine tonsil cancer, 4 underwent the combined approach of neck and oral resection and 1 with madibulotomy. All 5 patients with tongue base cancer received transhyoid partial glossotomy with or without partial laryngectomy. Sixteen patients with pyriform sinus carcinoma received partial laryngo-pharyngectomy with preservation of laryngeal functions. One patient with posterior hypopharyngeal wall carcinoma had partial pharyngectomy. Prognosis and laryngeal functions were analyzed after reconstruction surgery with submental artery perforator flap in patients with pharyngeal carcinoma. Results: The 27 patients were followed up for 6-66 months, with a median of 13 months, of them 24 patients were alive without recurrence or metastasis, 1 patient died of recurrence, 1 patient died of esophageal carcinoma and 1 patient was alive with the recurrence of tongue base carcinoma. Postoperative complications included flap failure for 1 case, pharyngeal fistula for 1 case, subcutaneous hydrops for 2 cases and lymphatic fistula for 1 case. Total 2 and 3 year survival rates were 92.9% and 88.9%, respectively. Total decanulation rate was 92.6%; decanulation rate and intubation time were 16/17 and 3.5 months in HPC patients; and decanulation rate and intubation time were 9/10 and 2 months in OPC patients. Total oral feeding rate was 92.6% and nasogastric feeding time was 3.5 weeks in HPC patients and 3 weeks in OPC patients. Conclusion: The submental artery perforator flap is an excellent choice for reconstruction surgery after removal of oropharyngeal and hypopharyngeal carcinoma, with good outcomes of laryngeal functions.

[A single-arm prospective study on induction chemotherapy and subsequent comprehensive therapy for advanced hypopharyngeal squamous cell carcinoma: report of 260 cases in a single center].

Objective: To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma. Methods: Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ(2)) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results: A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy (P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion: TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.

MicroRNA-548c-5p inhibits the proliferation of breast cancer cells through regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: The aim of this study was to explore the function of microRNA-548c-5p in breast cancer (BCa) and the underlying mechanism. Our findings might help to provide a theoretical basis for the diagnosis and treatment of BCa. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression level of microRNA-548c-5p in BCa tumor tissues and para-cancerous tissues. The relationship between microRNA-548c-5p expression and clinical indicators of BCa was analyzed. Meanwhile, the expression of microRNA-548c-5p in the BCa cells was detected by qRT-PCR as well. MicroRNA-548c-5p overexpression and the knockdown models were constructed in BCa cell lines MCF-7 and MDA-MB-231. Subsequently, Cell Counting Kit-8 (CCK-8), colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed to analyze the influence of microRNA-548c-5p on biological functions of BCa cells. Finally, the interaction between microRNA-548c-5p and Wnt/b-catenin signaling pathway was investigated. RESULTS: QRT-PCR results showed that the expression level of microRNA-548c-5p in BCa tumor tissues was remarkably lower than that of adjacent tissues, and the difference was statistically significant (p<0.05). Compared with patients with high expression of microRNA-548c-5p, the pathological stage of patients with low microRNA-548c-5p expression was significantly higher (p<0.05). Similarly, microRNA-548c-5p overexpression remarkably decreased the proliferation ability of BCa cells in vitro. However, microRNA-548c-5p knockdown showed an opposite trend. In addition, Wnt1, a key factor in the Wnt/b-catenin signaling pathway, was found remarkably up-regulated in BCa cell lines and tissues. Wnt1 expression was negatively correlated with microRNA-548c-5p expression. Western Blotting results demonstrated that microRNA-548c-5p mimics remarkably down-regulated the levels of the proteins in the Wnt/b-catenin signaling pathway. Conversely, opposite results were observed in microRNA-548c-5p inhibitor group. The rescue experiments in the cells revealed that there might be a mutual regulation between microRNA-548c-5p and Wnt1, thereby together regulating the malignant growth of BCa. CONCLUSIONS: MicroRNA-548c-5p was lowly expressed in BCa tissues and cells, which was closely related to the pathological stage of BCa. In addition, microRNA-548c-5p significantly inhibited the proliferation of BCa cells via modulating Wnt/b-catenin signaling pathway.

[Application of computer-assisted design and three-dimensional printing technique in reconstruction of maxillary defects with individual free fibular flap].

Objective: To evaluate the application of computer-assisted design and three-dimensional printing technique in reconstruction of maxillary defects with individual free fibular flap. Methods: A total of 13 patients, 7 males and 6 females with age from 12 to 55 years old, underwent the reconstruction of maxillary defects after subtotal or total maxillectomy for benign or malignant tumors between January 2016 and December 2018 were reviewed. Ther were 4 cases of subtotal maxillectomy and 9 cases of total maxillectomy. Before operation, osteotomy line was planned on three-dimensional images. A three-dimensional individual resin fibula model based on mirror images of the healthy side maxilla was obtained to fabricate an anatomically adapted osteomyocutaneous fibula free flap using computer-assisted design and forming. Oral, nasal, and eye functions and facial appearance were evaluated. Results: The 13 cases were followed up for 5-40 months, all flaps were alive except one due to flap failure and all cases were tumor free confirmed by CT or MRI. Ten patients could eat normal food without nasal food return, and 3 cases had palatal fistula. Eleven cases showed good speaking functional results. All cases had normal eye positions, no cases with diplopia and loss of vision. With evaluation by VAS, an average score of 8 was obtained, and most of patients were satisfied with their postoperative facial appearances. Conclusion: Reconstruction of maxillary defects by free fibular flap designed by three-dimensional printing and computer-assisted technique not only restored oral, nasal and eye functions, but also showed satisfactory facial appearance.

[Analysis for potential targeting genes of TPF regimen induction chemotherapy in hypopharyngeal squamous cell carcinoma].

Objective: To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Methods: Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. Results: A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01). Conclusion: CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.

Epidemics and aetiology of hand, foot and mouth disease in Xiamen, China, from 2008 to 2015.

Over the past 8 years, human enteroviruses (HEVs) have caused 27 227 cases of hand, foot and mouth disease (HFMD) in Xiamen, including 99 severe cases and six deaths. We aimed to explore the molecular epidemiology of HFMD in Xiamen to inform the development of diagnostic assays, vaccines and other interventions. From January 2009 to September 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription PCR that targeted the HEV 5' untranslated region and viral protein 1 region. Of these samples, 4290 were tested positive for HEV and the amplicons were sequenced and genotyped. Twenty-two genotypes were identified. Enterovirus 71 (EV71) and coxsackieviruses A16, A6 and A10 (CA16, CA6 and CA10) were the most common genotypes, and there were no changes in the predominant lineages of these genotypes. EV71 became the most predominant genotype every 2 years. From 2013, CA6 replaced CA16 as one of the two most common genotypes. The results demonstrate the vast diversity of HFMD pathogens, and that minor genotypes are able to replace major genotypes. We recommend carrying-out long-term monitoring of the full spectrum of HFMD pathogens, which could facilitate epidemic prediction and the development of diagnostic assays and vaccines.

[Simultaneous repairing defects of orbital floor and palate with the modified temporalis muscle flap after the maxillectomy].

Objective: To evaluate the outcome of one-stage reconstruction of maxillary and orbital defects with modified temporalis muscle flap (TMF) following the removal of malignant neoplasms. Methods: In this retrospective study, 15 patients underwent the reconstruction of defects of orbital floor and palate after maxillectomy for malignant tumor were included from June 2008 to June 2014. The modified temporalis muscle flap was used to repair the defects after surgery, and functional outcomes were analyzed. Results: All the patients were followed up for 12-81 months. Three cases of them received preoperative radiotherapy and 12 cases underwent postoperative radiotherapy. All flaps were survived. Epithelization of the tissues in oral and nasal cavity was completed in 4-6 weeks. Good functional reconstruction on swallowing and speaking functional results were achieved with maxillary and orbital reconstruction and no secondary deformity of external nose was observed. The eye positions in all cases were normal. Diplopia, diminution and loss of vision were not found. Conclusion: The modified TMF can be used for simultaneous reconstruction for the defects of orbital floor and palate after maxillectomy in patients whom free tissue flap can not be applied to, showing better cosmetic and functional results.

Nephrotic syndrome as a complication of chronic graft-versus-host disease after allogeneic haemopoietic stem cell transplantation.

Nephrotic syndrome (NS) is a rare complication following allogeneic haemopoietic stem cell transplantation (allo-HSCT), with limited current understanding of its pathogenesis. Here, we describe four cases of NS following allo-HSCT diagnosed at our institutions to identify key clinical and pathological features. In addition, a PubMed search was performed to identify existing reports that were pooled together with our cases for analysis. NS occurred as a late complication following allo-HSCT, with median onset 19.5 months after transplant (range: 3.9-84 months). The most common histopathology observed was membranous nephropathy; however, cases of minimal change disease have also been reported. There is a high incidence of prior extra-renal graft-versus-host disease (GvHD), with all four of our cases and 82% of published cases having prior GvHD. Glucocorticosteroids are the most common treatment, with variable degrees of response. Responses to immunosuppression with calcineurin inhibitors and rituximab have been described in steroid-refractory cases.

[Quantitative analysis of pathological voice and identification with artificial neural network].

Objective:To discuss the characteristic of the clinical pathological voice and the feasibility of computer automatic identification of pathological voice.Method:A total of 129 clinical patients with polyp of vocal cord were selected as the pathological voice group, while a total of 125 people with normal voice were selected from the community as the control group. Praat software was used to collect and analyze the related acoustic parameter values of two groups of cases, including Jitter, Shimmer, harmonic to noise ratio (HNR), signal to noise ratio (SNR), and normalized noise energy (NNE). Pathological voice group and control group were used as training set and testing set for neural network testing, and another 140 cases of pathological voice and normal voice data were selected as a validation set. SPSS Modeler was used for artificial neural network reconstruction to calculate the identification rate of pathological voice. Result:This study found according to the calculation of groups with different genders that Jitter, Shimmer and NNE were increased in pathological voice group compared with the normal group (P< 0.05), while HNR and SNR were decreased compared with the normal group (P< 0.05). Recognition rate of artificial neural network model on pathological voice is 75.7%.Conclusion:Objective voice analysis is helpful in the identification of pathological voice. Artificial neural network has higher accuracy in recognition of pathological voice, with good clinical application value.

Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC.

Acute myeloid leukemia (AML) is a biologically heterogeneous group of related diseases in urgent need of better therapeutic options. Despite this heterogeneity, overexpression of the interleukin (IL)-3 receptor α-chain (IL-3 Rα/CD123) on both the blast and leukemic stem cell (LSC) populations is a common occurrence, a finding that has generated wide interest in devising new therapeutic approaches that target CD123 in AML patients. We report here the development of CSL362, a monoclonal antibody to CD123 that has been humanized, affinity-matured and Fc-engineered for increased affinity for human CD16 (FcγRIIIa). In vitro studies demonstrated that CSL362 potently induces antibody-dependent cell-mediated cytotoxicity of both AML blasts and CD34(+)CD38(-)CD123(+) LSC by NK cells. Importantly, CSL362 was highly effective in vivo reducing leukemic cell growth in AML xenograft mouse models and potently depleting plasmacytoid dendritic cells and basophils in cynomolgus monkeys. Significantly, we demonstrated CSL362-dependent autologous depletion of AML blasts ex vivo, indicating that CSL362 enables the efficient killing of AML cells by the patient's own NK cells. These studies offer a new therapeutic option for AML patients with adequate NK-cell function and warrant the clinical development of CSL362 for the treatment of AML.

Antennapedia is involved in the development of thoracic legs and segmentation in the silkworm, Bombyx mori.

Homeotic genes, which are associated closely with body patterning of various species, specify segment identity. The Wedge eye-spot (Wes) is a new homeotic mutant located on the sixth linkage group. Homozygous Wes/Wes embryos are lethal and display a pair of antenna-like appendages under the mouthparts as well as fused thoracic segments. These mutants also exhibit a narrower eye-spot at the larval stage compared with the wild type. By positional cloning, we identified the candidate gene of the Wes locus, Bombyx mori Antennapedia (BmAntp). Two BmAntp transcripts were identified in the homozygote of the Wes mutant, including a normal form and an abnormal form with a 1570-bp insertion. Our data showed that the insertion element was a long interspersed nuclear element (LINE)-like transposon that destroyed the original open reading frame of BmAntp. Quantitative RT-PCR analysis showed that the expression levels of normal BmAntp transcripts were increased markedly in the Wes heterozygous larvae compared with the wild type. Furthermore, we performed RNAi of BmAntp and observed fused thoracic segments and defective thoracic legs in the developing embryos. Our results indicated that BmAntp is responsible for the Wes mutant and has an important role in determining the proper development of the thoracic segments. Our identification of a homeotic mutation in the silkworm is an important contribution to our understanding of the regulation of Hox genes at different levels of expression.

Effects of matrine, artemisinin, tetrandrine on cytosolic [Ca2+]i in guinea pig ventricular myocytes.

AIM: To compare the effects of matrine, artemisinin, and tetrandrine on intracellular Ca2+ concentration ([Ca2+]i) in guinea pig ventricular myocytes. METHODS: A single ventricular myocyte was loaded with Fluo 3-acetoxymethyl (Fluo 3-AM). [Ca2+]i was recorded by laser scanning confocal microscope and represented by fluorescence intensity (FI). RESULTS: 1) KCl 60 mmol . L-1 elevated the FI from 299 +/ -19 to 1389 +/- 325 (P < 0.01) in the presence of extracellular Ca2+ 1.8 mmol . L-1. 2) Both matrine and artemisinin at the concentration of 100 micromol . L-1 could enhance the increase of FI by KCl 60 mmol . L-1. The FI values reached 1495 +/- 320 and 1646 +/- 308 from 301 +/- 14 and 299 +/- 16 (P < 0.01), respectively. 3) Both tetrandrine 1, 10, and 100 micromol . L-1 and verapamil 10 micromol . L-1 inhibited the influx of extracellular Ca2+ induced by KCl 60 mmol . L-1. 4) Matrine 1, 10, and 100 micromol . L-1 could elevate the FI in the presence of extracellular Ca2+. The FI values reached 441 +/- 96, 504 +/- 112, and 643 +/- 126 from 303 +/- 27, 300 +/- 32, and 296 +/- 19 (P < 0.05), respectively. 5) Tetrandrine 1 and 10 micromol . L-1 could apparently inhibited Ca2+ release from intracellular calcium stores induced by caffeine 20 mmol . L-1 (P < 0.05). CONCLUSION: Effects of matrine, artemisinin, and tetrandrine on [Ca2+ )]i in ventricular