[Comparison of short-term and long-term outcomes between thoracoscopic pneumonectomy and open pneumonectomy for non-small cell lung cancer: a study based on propensity score matching].

Objective: To compare the short-term and long-term results of thoracoscopic and open pneumonectomy for non-small cell lung cancer. Methods: The clinical data of patients with non-small cell lung cancer who underwent pneumonectomy in the Department of Thoracic Surgery, Qingdao University Hospital from January 2008 to December 2016 were collected. Totally 142 patients (55 in the thoracoscopic group and 87 in the open group) were included in the study. A total of 29 pairs of patients were successfully matched by propensity score matching (PSM). Perioperative outcomes and overall survival were compared between the two groups using t test, χ(2) test, Kaplan-Meier curve and Log-rank test, respectively. Results: Camparion with open group, the thoracoscopic group had longer operative time ((209.7±70.2) minutes vs. (171.3±43.5) minutes, t=2.50, P=0.02), more mediastinal lymph node dissection (M(Q(R)): 17(9) vs. 11(10), W=388, P=0.02) and shorter postoperative hospital stay (7.0(3.5) vs. 9.0(3.0), W=285, P=0.03). There was no significant difference in estimated blood loss, postoperative drainage time, dissected lymph node number, dissected lymph node station and perioperative complications. After PSM, there were no signifificant differences found in 3-year survival (71.4% vs. 48.1%, P=0.10) and 3-year disease-free survival (67.4% vs. 47.2%, P=0.13) between the two groups. Conclusion: Thoracoscopic pneumonectomy is safe and feasible for the treatment of non-small cell lung cancer with more mediastinal lymph node dissection and accelerating recovery, and equivalent long-term prognosis when compared with open approach.

NGS-based profiling reveals a critical contributing role of somatic D-loop mtDNA mutations in HBV-related hepatocarcinogenesis.

BACKGROUND: Somatic mutations of mitochondrial DNA (mtDNA) have been extensively identified mainly by traditional Sanger sequencing technology in various cancer types. However, low detection sensitivity of traditional methods greatly limits the comprehensive profiling of mtDNA somatic mutations in cancers, especially in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Moreover, the functional roles of mtDNA mutation in HBV-related hepatocarcinogenesis have not been systematically revealed. PATIENTS AND METHODS: Next-generation sequencing (NGS) platform was applied to profile the somatic mtDNA mutations of HCC and paired paratumor (non-HCC) tissues from a large cohort of 156 HBV-HCC patients. RESULTS: Our data revealed the common existence of mtDNA mutation in both inflammatory and cancer tissues with significantly different mutation pattern. The mutation density (mutation number/region length) of D-loop region was much higher than that of other regions in both HCC and non-HCC tissues. Unexpectedly, the average mutation number in D-loop region of HCC tissues was significantly less than that of non-HCC tissues. In contrast, the heteroplasmy level of D-loop region mutations was significantly increased in HCC tissues, implying that the D-loop mutations might be positively selected in HCC tissues. Furthermore, our results indicated that the patients with D-loop mutations had a significantly lower mtDNA copy number and were more likely to relapse. In vitro experiments demonstrated that proliferation, invasion and metastasis ability of HCC cells with D-loop region mutations were significantly higher than those without D-loop region mutations. CONCLUSION: These results emphasize the critical contributing role of somatic mtDNA D-loop mutations in HBV-related hepatocarcinogenesis.

Tumour stiffness associated with tumour response to conventional transarterial chemoembolisation for hepatocellular carcinoma: preliminary findings.

AIM: To evaluate whether elastic (stiffness) characteristics of tumours were associated with treatment responses and survival of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolisation (TACE). MATERIALS AND METHODS: A retrospective cohort study of 59 HCC patients with unresectable HCC who underwent TACE was undertaken. Acoustic radiation force impulse imaging (ARFI) was used to measure tissue stiffness of the index tumours and non-tumoural liver before TACE treatment. The correlation between the parameters of tumour stiffness and treatment response to TACE was assessed using mRECIST criteria as well as according to patient survival. RESULTS: Tumour stiffness and its stiffness difference between tumour and non-tumoural liver were significantly associated with tumour response to TACE (p=0.019 and 0.010, respectively). Patients with tumour stiffness of <2 m/s or stiffness difference between tumour and non-tumoural liver of <0.5 were more likely to have treatment response to TACE. Univariate analysis showed that the difference in stiffness between tumour and non-tumoural livers (p=0.039) was one of the significant predictors of overall survival (OS). In multivariate analysis, alpha-fetoprotein (AFP) (p=0.006) and Barcelona Clinic Liver Cancer (BCLC) stage (p=0.017) were identified as independent predictors of survival. CONCLUSION: Tumour stiffness characteristics might be an added predictive marker of treatment response to TACE in patients with HCC.

Significance of platelet distribution width as a severity marker of erectile dysfunction.

Mean platelet volume (MPV) and Platelet distribution width (PDW) are potential markers in platelet activation. In present study, we aimed to evaluate MPV and PDW as potential severity markers for those patients who are complaining erectile dysfunction (ED). A total of 358 participants were enrolled in this study. The whole cohort was asked to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire. The participants were classified into 3 groups: control group (n = 120), mild ED (n = 118) and severe ED (n = 120). We found in our cohort MPV and PDW were significantly higher in both mild ED group and severe ED group than control group (9.24 ± 0.70 and 9.71 ± 0.80 versus 8.56 ± 0.62 for MPV; 14.48 ± 1.29 and 14.98 ± 1.60 versus 12.86 ± 1.13 for PDW respectively). The MPV and PDW increased as the disease progressed. In the mild and severe ED groups, a significant inverse correlation was detected between the mean values of IIEF-5 score and PDW. Furthermore, in the receiver operating characteristic curve analysis, the area under the curve of the MPV and PDW to predict severe ED was 0.818 and 0.848 respectively. Our study establishes a dose-dependent association between the PDW and ED. Therefore, the PDW can serve as a potential marker for predicting the severity of ED.

Ligation-assisted endoscopic enucleation for the treatment of colorectal submucosal tumours originating in the muscularis propria.

AIM: A ligation-assisted endoscopic enucleation (EE-L) technique was developed and was evaluated to determine its efficacy and safety for treating colorectal submucosal tumours (< 10 mm) originating in the muscularis propria. METHOD: EE-L was used to treat 13 patients between January 2011 and January 2014. The tumour was sucked into a transparent cap and ligated at its base by a rubber band ligature attached to the tip of the endoscope. With the creation of a pseudo-stalk, the tumour was then enucleated using endoscopic dissection and the wound was closed with clips. RESULTS: All tumours [median diameter 6.8 (4-10) mm] were successfully enucleated [procedure time 19 (11-27) min]. Histopathological examination identified 11 (84.6%) to be leiomyoma and 2 (15.4%) low-risk gastrointestinal stromal tumours. No perforations or massive haemorrhage occurred and there were no recurrences during a follow-up of 3-39 months. CONCLUSION: EE-L is a successful technique for the removal of small colorectal tumours in the muscularis propria with few complications and enables a histopathological diagnosis. In this study, all the resected lesions had a benign pathology.

Ligation-assisted endoscopic enucleation for treatment of esophageal subepithelial lesions originating from the muscularis propria: a preliminary study.

An innovative ligation-assisted endoscopic enucleation (EE-L) technique was developed for the diagnosis and treatment of esophageal subepithelial lesions (smaller than 12 mm) originating from muscularis propria by combining endoscopic band ligation and endoscopic enucleation techniques. The aim of the study was to evaluate efficacy and safety of EE-L technique in the treatment of esophageal subepithelial lesions (smaller than 12 mm) originating from muscularis propria. Forty-seven esophageal subepithelial lesions (smaller than 12 mm) originating from the muscularis propria in 44 patients were treated with EE-L between September 2010 and September 2012. The lesion was first aspirated into the transparent cap attached to the tip of endoscope. The elastic band was then released around its base. The purpose of ligation was to force the lesion to assume a polypoid form with a pseudostalk. Endoscopic enucleation was then performed until the tumor was completely enucleated from muscularis propria using a hook knife and forceps. All tumors (median diameter: 8.2 ± 2.3 mm, range: 4-12 mm) were enucleated completely. Histopathology identified 45 tumors (95.7%) as leiomyoma, 2 (4.3%) tumors as gastrointestinal stromal tumor with very low risk. The mean time of the EE-L procedure was 12.5 ± 4.6 minutes (range: 6-23 minutes). Two patients experienced self-limiting, non-life-threatening hemorrhage after EE-L. No perforation and massive hemorrhage requiring further endoscopic or surgical intervention occurred. There were no recurrences during the 6-24 months follow-up period. EE-L offers the option of localized treatment of small esophageal muscularis propria tumors (smaller than 12 mm) with relatively few complications and low mortality, and provides the advantage of allowing a histopathological diagnosis. All the resected lesions in this study had a benign pathology.

Transitional Dynamics of Sarcopenia and Associations of Nutritional Indices with State Transitions in Chinese aged ≥ 50.

OBJECTIVES: Sarcopenia's temporal profile can be regarded as a dynamic process with distinct states, in which malnutrition plays an important role. This study aimed to address two research gaps: sarcopenia's transitional dynamics and associations of nutritional indices with state transitions in community-dwelling Chinese adults aged 50 and older. DESIGN: A prospective population-based cohort study. SETTING: Community-based setting in western China. PARTICIPANTS: The analytic sample included data from 1910 participants aged ≥ 50 in the West China Health and Aging Trend study between 2018-2022. MEASUREMENTS: We defined three states: the initial normal state (normal muscle strength, physical performance and muscle mass), the worst sarcopenia state (low muscle mass plus low muscle strength and/or low physical performance) and the intermediate subclinical state (the other scenarios). The relevant measurement methods and cut-off points were based on the 2019 AWGS consensus. Using a continuous-time multistate Markov model, we calculated probabilities of transitions between different states over 1, 2 and 4 years; we also examined associations between nutritional indices and transitions, including body mass index (BMI), calf circumference (CC), mid-arm circumference (MAC), triceps skinfold thickness (TST), albumin (ALB), geriatric nutrition risk index (GNRI), vitamin D (VitD) and prealbumin (PA). RESULTS: For individuals in the normal state, their probabilities of remaining stable versus progressing to a subclinical state were 53.4% versus 42.1% at 2 years, and 40.6% versus 49.0% at 4 years. In the subclinical population, their 2- and 4-year chances were 60.2% and 51.2% for maintaining this state, 11.8% and 16.2% for developing sarcopenia, 28.0% and 32.6% for reverting to normal. For sarcopenic individuals, the likelihood of staying stable versus retrogressing to the subclinical state were 67.0% versus 26.3% at 2 years, and 48.3% versus 36.3% at 4 years. Increased BMI, CC, MAC, TST, ALB, GNRI and PA correlated with reversion from the subclinical state, among which increased TST, ALB and PA were also paralleled with reversion from sarcopenia, while decreased BMI, CC, MAC, TST and GNRI were associated with progression to sarcopenia. VitD was not significantly associated with any transitions. CONCLUSION: This study reveals how sarcopenia changes over time in a Chinese population. It also highlights the usefulness of simple and cost-effective nutritional status indices for indicating state transitions, which can help identify individuals at risk of sarcopenia and guide targeted interventions within the optimal time window.

Cohort Profile: West China Health and Aging Trend (WCHAT).

OBJECTIVES: The West China Health and Aging Trends study (WCHAT) is intended to focus on the research that will guide efforts to reduce disability, maximize health and independent functioning, and enhance quality of life at older ages in different ethnicities. And provide the basis for understanding trends and dynamics in late-life functioning, how these differ in various ethnic subgroups, and the economic or social consequences of aging and disability in western China. PARTICIPANTS: The cohort enrolled 7536 participants and 7439 participants aged 50 years and older in the baseline in 2018 and every year would be followed up. Finding to date: The data in WCHAT were prospectively collected from Yunnan, Guizhou, Sichuan and Xinjiang by 7 medical institutions. A number of age-related outcome measures were collected though corresponding geriatric assessments. Blood testing, saliva, urine and feces testing are available for all cohort participants. Future plans: The data in WCHAT can be used for various types of epidemiological research, particularly for examining how the culture specific life styles and diet influences geriatrics related outcomes. We are initially planning cohort studies and established a sample biobank in relation to the risk and prognosis of frailty, sarcopenia and other geriatric syndromes. Strengths and limitations of this study: It is a first multi-ethnic cohort study in West China that aimed to investigate the influence of culture specific life styles, diet and living environment on the prevalence of geriatric syndromes like frailty, sarcopenia and so on. This is a prospective multi-center observational study, which will be conducted in various ethnic groups gathering places. This study collected information that related to fatigue, falls, and cognition were obtained through self-reports, which might have recall bias and grouping errors. This study has problems such as the interviewees' refusal to visit, death, going out, and large population mobility may lead to high loss of visit rates. This study collected information from a comparatively healthier elderly population in which external validity was limited.

Upregulation of KCNMA1 facilitates the reversal effect of verapamil on the chemoresistance to cisplatin of esophageal squamous cell carcinoma cells.

OBJECTIVE: This study aimed to investigate the reversal effect of verapamil (VER) on the chemoresistance to cisplatin of esophageal squamous cell carcinoma (ESCC) cells. PATIENTS AND METHODS: The reversal effect of VER on cisplatin resistance in ESCC cells was evaluated via CCK-8 assay, colony formation assessment, and flow cytometry. The key genes that mediate this effect were screened via high-throughput transcriptome se¬quencing. The mRNA and protein expression levels of potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) in ESCC cells were examined via quantitative real-time PCR and Western blot analysis, respectively. The protein expressions of KCNMA1 in tissue samples from patients with either positive or negative responses to the therapeutic regimen of VER were determined via immunohistochemistry assay. Cell models with KCNMA1 knockdown and overexpression were es¬tablished to examine the role of KCNMA1 in mediating the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells. RESULTS: Results revealed that VER significantly decreased the 50% inhibitory concentration of cisplatin, inhibited colony formation, and induced apoptosis in ESCC cells. The curative effects of VER combined with chemotherapeutic drugs in KCNMA1-positive patients were better than those in KCNMA1-negative patients. KCNMA1 upregulation enhanced the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells. CONCLUSIONS: KCNMA1 facilitated the reversal effect of VER on cisplatin resistance in ESCC cells.

Three-dimensional assessment of root migration and rotation patterns after coronectomy: bone-embedded roots versus soft tissue-covered roots.

In this study, a three-dimensional evaluation was performed to explore differences between bone-embedded and soft tissue-covered roots after mandibular third molar (M3M) coronectomy. Patients were recruited according to the results of cone-beam computed tomography, 6 months after coronectomy. Completely bone-embedded M3Ms were assigned to group B, while completely soft tissue-covered M3Ms were assigned to group S. Data were recorded using digital software. A total of 213 M3Ms in 181 patients were investigated, of which 170 were assigned to the two study groups. Age was the primary factor influencing root migration (P<0.001). The smaller the degree of angulation of the M3M, the more likely was the root complex to rotate distally (r=-0.37, P<0.001). The depth of the impacted M3M contributed to the regeneration of new bone (P≤0.008). The length of the root complex (odds ratio 0.82, P=0.048) and distance from the root to the alveolar crest (odds ratio 1.23, P=0.026) were two critical factors influencing whether the root complex was bone-embedded. Ensuring that the length of the root complex is <7.6mm and the distance between the root and alveolar crest is ≥5mm were both found to be critical to the remaining root being completely bone-embedded and thus preventing eruption and the need for secondary surgery.

Prevalence and Its Associated Factors of Physical Frailty and Cognitive Impairment: Findings from the West China Health and Aging Trend Study (WCHAT).

OBJECTIVES: Previous literature has reported that physical frailty (PF) closely associated with cognitive impairment (CI). In this study, we aim to describe and evaluate the prevalence and associated factors with different patterns of PF and cognitive impairment. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: Community-dwelling older adults aged ≥60 from the West China Health and Aging Trend (WCHAT) study were included in this study. MEASUREMENTS: Participants were assessed the PF and cognitive impairment. PF was assessed using the physical phenotype as defined by Fried's criteria. Cognitive impairment was identified using the Short Portable Mental Status Questionnaire (SPMSQ). According different patterns of PF and cognitive impairment, participants were divided into 4 groups: not-PF and cognitive intact ( "neither" group), not-PF and cognitive impairment ("CI only" group), PF and cognitive intact ("PF only" group), and PF and cognitive impairment ("both" group). Multinomial logistic regression was used to explore the association between medical conditions and different patterns of PF and cognitive impairment after adjusting the demographic characteristics. RESULTS: Among 4,103 participants (age 67.8 + 5.9 years, female 58.3%), 78.8%, 3.9%, 14.5% and 2.9% were "neither", "PF only", "CI only", and "both", respectively. The prevalence of "PF only", "CI only" and "both" were associated with age, lower education level and single status. In addition, there was substantial ethnicity heterogeneity in the prevalence of different patterns of PF and cognitive impairment. Comparing with "neither", PF and/or cognitive impairment had higher association with depression, ADLs impairment, and malnutrition. Of note, obesity was only significantly associated with "PF only", but not associated with "CI only" or "both". CONCLUSIONS: We found the substantial demographic and medical conditions disparities in different patterns of PF and cognitive impairment. Further research should focus on the efficient and practical screen to predict the risk of "PF only", "CI only" and "both".

Sarcopenia, Obesity and Sarcopenia Obesity in Comparison: Prevalence, Metabolic Profile, and Key Differences: Results from WCHAT Study.

OBJECTIVE: To identify the prevalence, lifestyle factors, chronic disease status, and assessing the metabolic profile, comparing key differences in a cohort of subjects with non-sarcopenia/non-obesity (H), sarcopenia/non-obesity (S), non-sarcopenia/obesity (O) and sarcopenia obesity (SO) in a multi-ethnic population in west China. DESIGN: A cross-sectional study. SETTING: The communities in Yunnan, Guizhou, Sichuan, and Xinjiang provinces. PARTICIPANTS: We included 4,500 participants aged 50 years or older who did bioelectrical impedance in our analysis from West China Health and Aging Trend (WCHAT) study. MEASUREMENTS: We measured gait speed, handgrip strength and muscle mass by using bioelectrical impedance analysis (BIA) for all participants. We defined sarcopenia using the diagnostic algorithm recommended by the Asian Working Group for Sarcopenia (AWGS). Obesity was defined as the highest sex-specific quintile of the percentage body fat. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. Analysis of variance and a multinomial logistic regression analysis adjusting for covariates were used to assess the differences of metabolic profiles among different groups. RESULTS: Of 4500 participants aged 50 years old or older, the proportions of H, O, S, SO were 63.0%, 17.7%, 16.7% and 2.6%, respectively. And the prevalence of S subjects in men was 18.3% and 15.7% in women, while the prevalence of SO was 3.7% in men and 2.0% in women. Data showed that the prevalence of S and SO has an aging increase pattern which was opposite with O. Both S and SO tends to be older, lower educational level, without spouse, smoking, comorbidity of chronic disease, poor nutrition status, depression and cognitive decline compared to H and S seems to be worse than SO. Compared to H, S cohort showed a decrease in Vitamin D, triglyceride, albumin, fasting glucose, insulin, creatinine, ALT, nutrition scores and increase in HDL. SO cohort were observed for an increase in cholesterol, LDL, total protein and decrease in vitamin D. While O cohort showed an increase in triglyceride, cholesterol, LDL, total protein, glucose, insulin, WBC, uric acid, ALT and nutrition scores, but a decrease in HDL and vitamin D level. CONCLUSIONS: Among individuals aged 50 years old or older in West China. S, O and SO participants demonstrate distinct differences in the life-styles, chronic disease profile, and metabolic profiles. The prevalence of S and SO has an aging increase pattern contrary to O. Both S and SO tend to be older, lower educational level, without spouse, smoking, comorbidity of chronic disease, poor nutrition status, depression and cognitive decline compared to H and S looks like to be worse than SO. Besides, the S subjects seem to have more metabolic index changes than SO compared to H. While O subjects have some contrary metabolic index to S subjects.

The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system.

Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis in Alzheimer's disease.

Relieving phantom limb pain with multimodal sensory-motor training.

OBJECTIVE: The causes for the disabling condition of phantom limb pain (PLP), affecting 85% of amputees, are so far unknown, with few effective treatments available. Sensory feedback based strategies to normalize the motor commands to control the phantom limb offer important targets for new effective treatments as the correlation between phantom limb motor control and sensory feedback from the motor intention has been identified as a possible mechanism for PLP development. APPROACH: Ten upper-limb amputees, suffering from chronic PLP, underwent 16 days of intensive training on phantom-limb movement control. Visual and tactile feedback, driven by muscular activity at the stump, was provided with the aim of reducing PLP intensity. MAIN RESULTS: A 32.1% reduction of PLP intensity was obtained at the follow-up (6 weeks after the end of the training, with an initial 21.6% reduction immediately at the end of the training) reaching clinical effectiveness for chronic pain reduction. Multimodal sensory-motor training on phantom-limb movements with visual and tactile feedback is a new method for PLP reduction. SIGNIFICANCE: The study results revealed a substantial reduction in phantom limb pain intensity, obtained with a new training protocol focused on improving phantom limb motor output using visual and tactile feedback from the stump muscular activity executed to move the phantom limb.

Endoscopic ultrasound-guided interstitial chemotherapy in the pancreas: results in a canine model.

BACKGROUND AND STUDY AIM: Interstitial chemotherapy using surgically implanted, biodegradable polymers has been reported. Our aim in this study was to investigate the feasibility and safety of endoscopic ultrasound- (EUS-) guided interstitial chemotherapy of the pancreas in a canine model. MATERIALS AND METHODS: A therapeutic 19-gauge needle with a large channel was inserted into the pancreas under EUS guidance. The polymers for sustained intratumoral release of 5-fluorouracil were implanted into the tissue by the needle. After 14 days of clinical observation, the animals were sacrificed and the tissue response to the local chemotherapy was examined. RESULTS: All the polymers were implanted successfully and no implant migration occurred. Localized tissue fibrous necrosis was achieved in the pancreas, without significant complications. The apoptotic index of the tissue within 1 cm of the focus increased. Biochemical parameters were normal in all the dogs. CONCLUSIONS: EUS-guided implantation of polymers is a safe, simple, and minimally invasive technique for interstitial chemotherapy in the pancreas.

Partial sialoadenectomy for the treatment of benign tumours in the submandibular gland.

The conventional treatment for benign tumours arising in the submandibular gland (SMG) has always involved whole gland excision with the tumour. In light of developments in parotid gland functional surgery, this prospective study was performed to evaluate the effectiveness and safety of partial sialoadenectomy (PS) for benign tumours in comparison with conventional total sialoadenectomy (TS). Thirty-one consecutive patients with a preoperative diagnosis of benign tumour in the SMG were included in the study from December 2008 to December 2010. Eleven patients were treated with PS and 20 patients underwent conventional TS. Salivary gland function and surgery-related complications were assessed. No difference in resting saliva flow was found between the two groups before the operation, while this was significantly higher in the PS group than in the TS group at 1 year after surgery (P=0.009). With regard to complications, there was less deformity in facial appearance in the PS group. There was no recurrence in any of the 31 patients during the follow-up period (range 41-82 months). It is believed that this modification to SMG surgery is consistent with the idea of functional and minimal invasive salivary gland surgery. This technique represents a good choice for the management of benign tumours of the SMG for appropriately selected cases.

[Accuracy and reliability of three-dimensional craniofacial cone-beam CT superimposition method based on voxel registration].

OBJECTIVE: To set up a three-dimensional(3D)craniofacial cone-beam CT(CBCT)superimposition method based on voxel registration, and evaluate the accuracy and reliability of different reference superimposition areas. METHODS: CBCT scans were taken on a dry skull for three times with a time-interval of two weeks, and CBCT scans were taken on ten adult volunteers twice with a time-interval of one month. The 3D superimposition based on voxel registration was set up by means of Analyze 12.0. The bilateral-zygomatic bone and anterior cranial base were selected as different reference areas for voxel overlapping. The 3D overlapping images were output into Geomagic Qualify 2013, and the surface distances on different craniofacial regions were measured. Three operators repeated three times of these superimposition and measurement. SPSS 19.0 were used to analyze the accuracy and reliability. RESULTS: When bilateral-zygomatic bone used as superimposition reference, the mean surface distance range of dry skull were from 0.035 to 0.064 mm, and volunteers from 0.099 to 0.182 mm. When the anterior cranial base used as superimposition reference, the mean surface distance range of dry skull were from 0.038 to 0.071 mm, and volunteers from 0.127 to 0.218 mm. All these mean values were less than the CBCT voxel size 0.25 mm(P<0.05), and got sub-pixel precision. No significant difference was found between the different operators at different times(P>0.05). CONCLUSIONS: This study showed the high accuracy and reliability of 3D CBCT superimposition based on voxel registration, either the anterior cranial base or the bilateral-zygomatic bone as reference. This method could be used for evaluating 3D craniofacial treatment effects.

Expression of PTEN in PTEN-deficient multiple myeloma cells abolishes tumor growth in vivo.

Biochemical abnormalities associated with the development of multiple myeloma have been difficult to define especially in terms of demonstrating an in vivo effect of suspected lesions. Herein, we have identified such a defect associated with lack of expression of PTEN, a cellular phosphatase involved in the regulation of phosphatidylinositol phosphates (PIP's). In myeloma cells, PIP's are required for phosphorylation of Akt, a key event leading to inhibition of apoptosis. Loss of PTEN results in a failure to de-phosphorylate PIP's and a corresponding increase in Akt phosphorylation. OPM-2 cells lacking PTEN expression have the highest level of Akt phosphorylation of eight lines examined. Loss of PTEN was found to be associated with a 630 bp deletion corresponding to amino acids 56 - 267. Ectopic expression of wild type PTEN in OPM-2 cells inhibited Akt phosphorylation which was correlated with an increase in apoptosis. The in vivo relevance of loss of PTEN expression was demonstrated by injecting control and wild type PTEN transfected OPM-2 cells into SCID mice. Tumors arose at an incidence of 100% in controls, but only 50% (and of smaller size and longer latency) in low PTEN expressing clones. Importantly, clones expressing high levels of PTEN failed to produce tumors even at five times the latency period of controls. These results demonstrate that PTEN deletion/mutation is responsible for in vivo growth of this tumor and suggests that PTEN regulation may play an important role in tumor development in a subset of multiple myeloma patients. Oncogene (2000) 19, 4091 - 4095