[Transoral robotic thyroidectomy via vestibular approach: a retrospective study of 107 cases in a single center].

Objective: To investigate the short-term outcome of transoral robotic thyroidectomy. Methods: This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960th Hospital of People's Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results: All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized (M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection (n=1), left submandibular perforation (n=1), skin scald (n=1), and perioral numbness (n=1), oral tear (n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion: For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

[A family with early onset myopathy caused by MEGF10 gene defect and literature review].

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.

[A retrospective comparative study between robotic thyroidectomy through transoral vestibular approach and bilateral breast-axillary approach].

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t=6.915, P<0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t=-3.544, P=0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t=-2.353, P=0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t=2.925, P=0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P>0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.

[Preliminary application of transoral robotic thyroidectomy: experience from an initial 30 cases].

Objective: To examine the surgical outcome of transoral robotic thyroidectomy. Methods: Clinic data of total 30 cases of transoral robotic thyroidectomy at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from May 2020 to December 2020 were analyzed retrospectively. There were 3 males and 27 females, aged (31.5±11.0) years (range: 17 to 55 years), including 6 cases of benign tumor and 24 cases of malignant cancer (all papillary thyroid carcinoma). An inverted U-shaped incision 1.5 cm in length was made over the end of the frenulum of the lower lip. A wide subplatysmal space was created by bluntly passing with a vascular tunneller (8 mm diameter), and a 12 mm trocar was inserted through the lip incision for the camera port. Lateral oral mucosal incisions 8 mm in length were made near both lateral labial commissures, 8 mm robot trocars were inserted through the incisions. An 5 mm trocar was inserted through an incision made along the patient's right axillary fold into the subplatysmal working space and was connected with 5 mm ProGrasp for counter traction during the operation and for later drain insertion. Numerical scoring system (NSS) was used to assess cosmetic effect 1 month post-operation. Results: All the 30 transoral robotic thyroidectomies was successful, no case conversed to open operation. Postoperative hospital stay was (6.3±1.2) days (range: 4 to 10 days). The tumor size of thyroid cancers was (5.3±3.0) mm (range: 2 to 15 mm). Lymph node metastasis was observed in 12 cases. The retrieved central lymph node number was 10.5±4.4 (range: 4 to 20), while the central metastatic lymph node number was 2(2) (range: 1 to 11). Postoperative transient hypoparathyroidism occurred in 2 cases. Permanent hypoparathyroidism and vocal cord palsy didn't occur. Other surgical complications included hematoma, surgical site infection and perforation of chin flap, retrospectively in 1 case. Local regional lymph node recurrence wasn't developed during 1 to 7 months follow-up. All patients were satisfied with the postoperative cosmetic outcomes,NSS was 9.4±0.8 (range: 8.7 to 9.6). Conclusion: Transoral robotic thyroidectomy is safe and effective, suitable for early thyroid cancers without lateral lymph node metastasis, and has superior cosmetic results when the patients are selected carefully.

[Outcomes of 1 000 cases of robotic thyroidectomy by bilateral axillo-breast approach: a retrospective study in a single center].

Objective: To examine the surgical outcome, completeness and safety of robotic thyroidectomy by bilateral axillo-breast approach (BABA). Methods: From February 2014 to May 2019, 1 000 cases of robotic thyroidectomy via BABA at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army were performed. The clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes of patients underwent robotic thyroidectomy were collected and reviewed retrospectively. There were 216 males and 784 females, aging (42.3±11.5) years (range: 7 to 75 years). There were 270 cases with benign tumors, and 730 cases with malignant cancers (the tumor diameter was (7.9±6.7) mm (range: 0.1 to 60.0 mm)). Results: There were 999 patients received robotic thyroidectomy using BABA approach successfully, while only 1 case conversed to open operation. The postoperative hospital stay was (7.5±2.5) days (range: 2 to 30 days). Among the 730 patients with thyroid cancers, 725 cases (99.3%) were papillary thyroid carcinoma, 579(79.3%) cases were with papillary thyroid microcarcinoma. Lymph node metastasis was observed in 371(50.8%) cases. The retrieved central lymph node number was 11.2±6.1 (range: 1 to 44),and the retrieved lateral lymph node number was 14.0±8.8 (range: 1 to 52). Postoperative transient hypoparathyroidism and vocal cord palsy occurred in 247(24.70%) and 56(5.60%) cases. Both of permanent hypoparathyroidism and vocal cord palsy occurred in 2 (0.20%) cases. Other surgical complications included chyle leakage (6.1%, 28/460), trachea injury (0.40%, 4/1 000), carotid artery injury (0.10%, 1/1 000). Local regional lymph node recurrence was developed in 4 patients. All patients were satisfied with the postoperative cosmetic outcomes. Conclusions: Robotic thyroidectomy by BABA is safe and effective, suitable for large benign tumors and early thyroid cancers with central or lateral lymph node metastasis. It could obtain superior cosmetic results.

[Application of da Vinci robot's bilateral axillo-breast approach in thyroid surgery of obese patients].

Objective:To discuss the effect of obesity on the operation of thyroid gland surgery and surgical results.Method:The clinical data of 446 patients who underwent robot thyroid surgery through bilateral axillo-breast approach (BABA) from the General Hospital of Jinan Military region from February 2014 to November 2017 were analyzed retrospectively, and the patients were divided into BMI<25 kg/m²; group, BMI 25-30 kg/m²; group and BMI>30 kg/m²; group according to body mass index (BMI). The operative complications were compared between the three groups of benign and malignant patients, such as operation time, postoperative lead flow, postoperative hospitalization time, tumor size (malignant), lymph node metastasis (malignant), cosmetic satisfaction score, laryngeal nerve injury and parathyroid function decrease. Statistical methods using Variance analysis and χ² test to compare the differences between the two groups of indicators, difference is statistically significant (P<0.05).Result:The difference of operation time, postoperative average hospitalization time and postoperative drainage fluid volume in 3 groups was not statistically significant（P>0.05）. ①Intraoperative and postoperative pathological results were benign: BMI<25 kg/m²; group 69 cases, BMI 25-30 kg/m²; group 48 cases, BMI>30 kg/m²; group 8 cases, temporary recurrent laryngeal nerve injury were 1 case, 0 case and 0 case respectively, temporary parathyroid function decrease 3 cases, 2 cases and 1 case. ②Intraoperative and postoperative pathological results were malignant:BMI<25 kg/m²; group 180 cases, BMI 25-30 kg/m²; group 119 cases,BMI>30 kg/m²; group 22 cases, temporary recurrent laryngeal nerve injury were 2 cases,1 case and 0 case respectively, temporary parathyroid dysfunction in 64 cases,29 cases and 5 cases respectively.③1 patient in BMI<25 kg/m²; group had lymphatic leakage after operation, 1 patient in BMI 25-30 kg/m²; group had subcutaneous tunnel hemorrhage, and 1 patient had lymphatic leakage during operation.Conclusion:For overweight or obese patients, the da Vinci robot thyroid operation is reliable, does not increase the risk of surgical complications, but also has a good cosmetic effect.

[BABA of da Vinci robot thyroid surgery in the standard treatment of thyroid cancer surgery].

Thyroid cancer is the most common malignant tumor in endocrine surgery. Surgery is the first choice for most patients with thyroid cancer. Da Vinci robot system as the auxiliary system is the most advanced endoscopic surgery, largely to fill the cavity mirror device cannot bend, complex operation and so on insufficiency, has now become an important way of surgical treatment of thyroid cancer, and its curative effect, high safety, but because of the economic cost is higher, is currently not widespread popularity.

Real-Time Motor Cortex Mapping for the Safe Resection of Glioma: An Intraoperative Resting-State fMRI Study.

BACKGROUND AND PURPOSE: Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation. MATERIALS AND METHODS: Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex. RESULTS: Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (P = .049). However, no significant difference between the anesthesia types was observed (P = .102). CONCLUSIONS: This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.

Early inhaled nitric oxide in preterm infants <34 weeks with evolving bronchopulmonary dysplasia.

OBJECTIVE: To investigate whether early treatment with inhaled nitric oxide (iNO) could prevent bronchopulmonary dysplasia (BPD) in very preterm infants. STUDY DESIGN: A non-randomized, controlled trial was conducted prospectively in 27 neonatal intensive care units over 12 months. Preterm infants with gestational age <34 weeks and after 7 days of life, who received invasive mechanical ventilation (MV) or nasal continuous positive airway pressure for >2 days, were treated either with low-dose iNO (from 5 as initial dose to 2 parts per million as maintenance dose for ⩾7 days, n=162) or as non-placebo control (n=240). Primary outcome was the incidence of moderate-to-severe BPD at 36 weeks postmenstrual age and/or death before discharge. Secondary outcomes were major complications. RESULTS: iNO was started on average on day 19 of life (median duration 18 days, range 7 to 55 days). Rate of survival without BPD was significantly lower in the iNO than in the control group, whereas overall rates of BPD, death and major complications were similar between the two groups. Infants who started MV and iNO on postnatal days 15 to 21 had significantly increased survival without BPD (47.6% vs 17.1%, P=0.03, relative risk 2.7, 95% confidence interval 1.1 to 6.5). Additionally, pooled data from both groups showed that rates of perinatal co-morbidities and postnatal complications were higher in BPD infants than in non-BPD infants. The overall incidence of BPD was 55.6% and 75.9% for birth weight <1500 and <1000 g, respectively, or 1.6% for the total population <34 weeks of gestation admitted through the network. CONCLUSION: Treatment with low-dose iNO did not decrease the overall risk of BPD and death nor showed adverse effects in short-term morbidities among very preterm infants. The benefit of delayed iNO treatment on BPD warrants further studies.

Cross-sectional survey on public health informatics workforce in China: issues, developments and the future.

OBJECTIVE: To explore the current situation and issues related to the development of the public health informatics (PHI) workforce in provincial and prefectural centers for disease control and prevention (CDCs) in China, and to describe the corresponding strategies to address these issues for the future. STUDY DESIGN: National cross-sectional study. METHODS: One thousand two hundred and eighty-one respondents were selected at random from provincial and prefectural CDCs. The survey used a self-administered, structured questionnaire with an online data collection tool that integrated data quality control and user management. The questionnaire was divided into seven main categories. Score percentage of satisfaction and proportion in each part were calculated. Descriptive statistics were used to analyse the data, stratifying by country region, CDC level, job role and educational level. RESULTS: One hundred and sixty staff from provincial CDCs and 1121 staff from prefectural CDCs were selected. Only 7.4% (33/445) of prefectural CDCs were not involved in this survey, due to lack of PHI practitioners. CDC staff in the eastern region were predominantly aged 30-39 years (39.5%), which was much younger compared with the other regions (P = 0.0012). Only 34 respondents (2.7%) had academic majors in both health and information technology. More staff had Master's degrees and a higher level of education (18.7%) in the eastern region compared with the other regions (P < 0.0001). Staff in the eastern region in high-level positions and with a higher level of education were more knowledgeable about PHI strategy. Prefectural CDC staff were more satisfied with their work and training than provincial CDC staff. In the eastern region, 34.9% of staff were hired through competitive recruitment, and 57.8% of staff had received a job description with detailed information about their responsibilities, which was higher than in the other regions. Staff in the western region were more likely to leave if a better job became available (37.7%) compared with staff in the other regions (P = 0.0116). CONCLUSION: This study found regional disparities in PHI workforce development, possibly related to disparities in overall regional development. Findings showed a severe shortage of staff with a background in PHI, and occupational development paths were clearly lacking. Based on this study of current workforce issues, a comprehensive strategy for PHI workforce development in China has been described.

Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy.

Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrP(TME) and of which only the HY strain is associated with accumulation of PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrP(TME) in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum, after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrP(TME) was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrP(TME) was detected readily in the brain and retropharyngeal lymph node during preclinical infection, with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrP(TME) in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrP(TME) accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrP(TME) in the lymphoid tissues of mink but not in hamsters. Thus, mink are a relevant animal model for further study of this unique strain, which ultimately may have been introduced through consumption of a TSE of ruminant origin.

PP2A-B56α controls oncogene-induced senescence in normal and tumor human melanocytic cells.

Oncoprotein C-MYC is overexpressed in human metastatic melanomas and melanoma-derived cells where it is required for the suppression of oncogene-induced senescence (OIS). The genetic events that maintain high levels of C-MYC in melanoma cells and their role in OIS are unknown. Here we report that C-MYC in cells from several randomly chosen melanoma lines was upregulated at the protein level, and largely because of the increased protein stability. Of all known regulators of C-MYC stability, levels of B56α subunit of the PP2A tumor suppressor complex were substantially suppressed in all human melanoma cells compared with normal melanocytes. Accordingly, immunohistochemical analysis revealed that the lowest and the highest amounts of PP2A-B56α were predominantly detected in metastatic melanoma tissues and in primary melanomas from patients with good clinical outcome, respectively. Importantly, PP2A-B56α overexpression suppressed C-MYC in melanoma cells and induced OIS, whereas depletion of PP2A-B56α in normal human melanocytes upregulated C-MYC protein levels and suppressed BRAF(V600E)- and, less efficiently, NRAS(Q61R)-induced senescence. Our data reveal a mechanism of C-MYC overexpression in melanoma cells and identify a functional role for PP2A-B56α in OIS of melanocytic cells.

Influence of traditional Chinese medicine on spermatozoa infected in vitro with Escherichia coli.

Escherichia coli (E. coli) is the most common cause of urogenital infection and is implicated in genesis of male infertility. In this in vitro study, the influence of traditional Chinese medicine (TCM)-Qinglishengjing pills on spermatozoa infected in vitro with E. coli was studied. Semen samples were prepared by standard technique and sperm suspension was coincubated respectively with E2888 EARLE'S (group A as normal control), E. coli suspension (group B), mixture of E. coli suspension and TCM (group C) and mixture of E. coli suspension and Furadantin (group D) in vitro. After coincubation, motility parameters, phosphatidylserine (PS) externalisation and morphology of spermatozoa were evaluated. No significant difference between the group C and group A was found in sperm motility parameters (P > 0.05), whereas difference between group B and group A was significant after 2 h (P < 0.05) and 4 h (P < 0.01). Mixed agglutination and ultrastructure damage could be observed in group B and no apparent similar agglutination and ultrastructure damage were observed in other groups. There was no difference in PS externalisation per cent between the groups A and C (P > 0.05) and there was significant difference between the groups A and D, A and B, B and D, C and D (P < 0.01). TCM-Qinglishengjing pills could reverse E. coli effects on spermatozoa in vitro.

A sparse intraoperative data-driven biomechanical model to compensate for brain shift during neuronavigation.

BACKGROUND AND PURPOSE: Intraoperative brain deformation is an important factor compromising the accuracy of image-guided neurosurgery. The purpose of this study was to elucidate the role of a model-updated image in the compensation of intraoperative brain shift. MATERIALS AND METHODS: An FE linear elastic model was built and evaluated in 11 patients with craniotomies. To build this model, we provided a novel model-guided segmentation algorithm. After craniotomy, the sparse intraoperative data (the deformed cortical surface) were tracked by a 3D LRS. The surface deformation, calculated by an extended RPM algorithm, was applied on the FE model as a boundary condition to estimate the entire brain shift. The compensation accuracy of this model was validated by the real-time image data of brain deformation acquired by intraoperative MR imaging. RESULTS: The prediction error of this model ranged from 1.29 to 1.91 mm (mean, 1.62 ± 0.22 mm), and the compensation accuracy ranged from 62.8% to 81.4% (mean, 69.2 ± 5.3%). The compensation accuracy on the displacement of subcortical structures was higher than that of deep structures (71.3 ± 6.1%:66.8 ± 5.0%, P < .01). In addition, the compensation accuracy in the group with a horizontal bone window was higher than that in the group with a nonhorizontal bone window (72.0 ± 5.3%:65.7 ± 2.9%, P < .05). CONCLUSIONS: Combined with our novel model-guided segmentation and extended RPM algorithms, this sparse data-driven biomechanical model is expected to be a reliable, efficient, and convenient approach for compensation of intraoperative brain shift in image-guided surgery.

C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells.

Malignant melanomas often harbor activating mutations in BRAF (V600E) or, less frequently, in NRAS (Q61R). Intriguingly, the same mutations have been detected at higher incidences in benign nevi, which are largely composed of senescent melanocytes. Overexpression of BRAF(V600E) or NRAS(Q61R) in human melanocytes in vitro has been shown to induce senescence, although via different mechanisms. How oncogene-induced senescence is overcome during melanoma progression remains unclear. Here, we report that in the majority of analysed BRAF(V600E)- or NRAS(Q61R)-expressing melanoma cells, C-MYC depletion induced different yet overlapping sets of senescence phenotypes that are characteristic of normal melanocytes undergoing senescence due to overexpression of BRAF(V600E) or NRAS(Q61R), respectively. These senescence phenotypes were p16(INK4A)- or p53-independent, however, several of them were suppressed by genetic or pharmacological inhibition of BRAF(V600E) or phosphoinositide 3-kinase pathways, including rapamycin-mediated inhibition of mTOR-raptor in NRAS(Q61R)-expressing melanoma cells. Reciprocally, overexpression of C-MYC in normal melanocytes suppressed BRAF(V600E)-induced senescence more efficiently than NRAS(Q61R)-induced senescence, which agrees with the generally higher rates of activating mutations in BRAF than NRAS gene in human cutaneous melanomas. Our data suggest that one of the major functions of C-MYC overexpression in melanoma progression is to continuous suppress BRAF(V600E)- or NRAS(Q61R)-dependent senescence programs.

c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle.

A major role for c-Myc in the proliferation of normal cells is attributed to its ability to promote progression through G(1) and into S phase of the cell cycle. The absolute requirement of c-Myc for cell cycle progression in human tumor cells has not been comprehensively addressed. In the present work, we used a lentiviral-based short hairpin RNA (shRNA) expression vector to stably reduce c-Myc expression in a large number of human tumor cell lines and in three different types of normal human cells. In all cases, cell proliferation was severely inhibited, with normal cells ultimately undergoing G(0)/G(1) growth arrest. In contrast, tumor cells demonstrated a much more variable cell cycle response with cells from several lines accumulating in S or G(2)/M phases. Moreover, in some tumor lines, the phase of cell cycle arrest caused by inhibition of c-Myc could be altered by depleting tumor suppressor protein p53 or its transcriptional target p21(CIP/WAF). Our data suggest that, as in the case of normal cells, c-Myc is essential for sustaining proliferation of human tumor cells. However its rate-limiting role in cell cycle control is variable and is reliant upon the status of other cell cycle regulators.

Variable patterns of distribution of PrP(CWD) in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease.

Sections of medulla oblongata, taken at the level of the obex, palatine tonsil and medial retropharyngeal lymph node from 10,269 captive Rocky Mountain elk (Cervus elaphus nelsoni), were examined by immunohistochemical staining with monoclonal antibody for the prion protein associated with the transmissible spongiform encephalopathy of cervids, chronic wasting disease (PrP(CWD)). The protein was detected in 226 of them. On the basis of the anatomical location of the deposits in the brainstem of 183 elk, four distinct patterns of distribution of PrP(CWD) within the parasympathetic region of the dorsal motor nucleus of the vagus nerve and the adjacent nuclei were observed. Mild gross lesions of chronic wasting disease (serous atrophy of fat) were observed in only three elk, all with spongiform degeneration; the other elk were considered to be in the preclinical stage of the disease. In contrast with the relatively predictable distribution of prion protein (PrP) in the brain and cranial nodes of sheep and mule deer, the distribution of PrP(CWD) in the brain and nodes of the elk was more variable and unrelated to their PrP genotype. One hundred and fifty-five of the 226 positive elk had deposits of PrP(CWD) in the brainstem and lymphoid tissues, 43 had deposits only in the lymphoid tissue and 28 had deposits only in the brainstem.