Comprehensive evaluation of factors that induce gingival enlargement during orthodontic treatment: A cross-sectional comparative study.

BACKGROUND: Gingival enlargement (GE) is one of the most common soft tissue problems encountered during fixed orthodontic treatment. Aims: This study aimed to evaluate the factors affecting GE in adolescents and young adults, compared with their normal peers. SUBJECTS AND METHODS: This is a cross-sectional comparative study. The sample consisted of 329 subjects (ages 10-30 years) of both genders, which was divided into four main groups: The control group (G0) with no orthodontic treatment; subjects who underwent orthodontic treatment were divided according to treatment duration into G1 (4-12 months), G2 (13-24 months), and G3 (>24 months). The clinical examinations included the level of debris, calculus (simplified oral hygiene), and GE indices. Regression analyses were used to assess the GE association in all the studied groups. RESULTS: The mean GE score increased significantly with increased treatment duration (0.42 ± 0.29 for G0 and 1.03 ± 0.52 for G3). GE scores of the lower arch were significantly higher in the anterior segment than in the posterior segment among all treatment groups. Regression analysis revealed that gender, age, oral hygiene, and treatment duration had a significant effect on GE (P < 0.05), while angle classification, overjet, overbite, treatment stage, bracket type, and therapeutic extraction did not show significant associations (P > 0.05). CONCLUSION: Gender, age, oral hygiene, and treatment duration were the most important risk factors for GE during fixed orthodontic treatment.

[Gene analysis and clinical features of MYH9-related disease].

Objective: To identify gene variants and investigate clinical features of nonmuscle myosin heavy chain 9-related disease (MYH9-RD). Methods: In this retrospective study, the data of patients with MYH9-RD admitted to Shenzhen Children's Hospital from July 2017 to September 2020 were extracted. The gene variants, clinical features and laboratory tests results were summarized. Results: Among the 6 children, 4 were males and 2 were females, aged 4.0 (0.5-7.6) years. Main clinical manifestations included thrombocytopenia (6 cases), epistaxis (3 cases), petechias (2 cases), traumatic hematoma (1 case), and abnormal liver enzymes (1 case). One patient had no family history, and the other 5 cases were pedigrees. Two pedigrees (2 cases) had long-term microscopic hematuria, one pedigree (2 cases) had history of early cataract, and three pedigrees (5 cases) had chronic mild elevation of liver enzymes. Four MYH9 gene variants were found in 12 patients, including c.2104C>T(p.R702C) in exon 17, c.4270G>A(p.D1424N) in exon 31, c.5521G>A (p.E1841K) in exon 39, and c.5797C>T (p.R1933X) in exon 41. According to the family pedigrees analysis, except for the case of variant in exon 17 which was spontaneous mutation with no family history, the other variants were from their father or mother. The complete blood count results showed a decreased platelet number in these patients, and the counting results of the automated hematology analyzer were significantly lower than that of manual counting method ((33.4±17.2) × 109 vs. (60.4±21.0) × 109/L,t=-5.83, P<0.05). The examination of the peripheral blood smear revealed the presence of thrombocytopenia with giant platelets and granulocyte inclusion bodies. The MYH9 gene variant (R702C) located at the N-terminus head domain of non-muscle myosin heavy chain ⅡA (NMMHC-ⅡA), which has ATPase activity, led to severe reduction of platelet number (<20×109/L) and obscure granulocyte inclusion bodies. However, higher platelet numbers (40×109-80×109/L) and obvious granulocyte inclusion bodies were observed in patients with tail-position mutations at C-terminus. Conclusions: The clinical phenotypes of MYH9-RD were variable. The mutations in certain regions of MYH9 gene were related to platelet count and granulocyte inclusion bodies. MYH9-RD should be considered in individuals with unknown etiology and persistent thrombocytopenia which is non-responsive to conventional treatment, regardless of family history. Complete blood count and blood smear morphology examinations are the first steps to screen and diagnose the disease. The laboratory should pay attention to the morphological review rules and standardized reports.

Insights into the novel function of system Xc- in regulated cell death.

System Xc-, also named cystine/glutamate antiporter, is an important intracellular antioxidant element. It is composed of the light chain SLC7A11 (xCT) and the heavy chain SLC3A2 (4F2hc) and functions as raw materials for the synthesis of glutathione (GSH). Recent studies have demonstrated that system Xc- plays an important role in different types of regulated cell death, which is referred to cell death controlled by dedicated molecular machinery. It has been shown that system Xc- involves in ferroptosis, apoptosis, and autophagy-dependent cell death, contributing to different diseases and drug resistance, such as cancer, neurological disorders, and cisplatin resistance to cancers. To date, the intervention of system Xc- by its inhibitors or activators displays a beneficial effect on the treatment of certain diseases. In this review, we summarize recent findings on the role of system Xc- in regulated cell death, including molecular mechanisms and potential therapeutic applications.

[Preclinical application of MR and fluorescent dual-modality imaging combined with photothermal therapy in HER-2 positive breast cancer].

Objective: To construct superparamagnetic iron oxide nanoparticles (SPIONs) coated on trastuzumab and indocyanine green (ICG) and then investigate whether the coated nanoparticles (NPs) targeted to human epidermal growth factor receptor-2 (HER-2) receptors on breast cancer cells in vitro and in vivo. Methods: The Fe(3)O(4)-trastuzumab-ICG NPs were constructed. And a series of characteristics of the NPs were evaluated. The uptake ability of SK-BR-3, a HER-2 positive breast cancer cell, was observed by transmission electron microscopy. Then the NPs were injected in the tail veins of SK-BR-3 xenograft tumor-bearing mice to observe the aggregation of NPs in the tumor sites by MRI and fluorescent imaging. Furthermore, when the NPs was gathered at the tumor sites, the near infrared thermal imaging system was used to monitor the tumor temperature after the near infrared radiation. Results: The successfully constructed Fe(3)O(4)-trastuzumab-ICG NPs had the size of (25.93±4.25) nm. The absorption peak was 828 nm, which was as same as the emission wavelength of ICG. The NPs had a high relaxation rate of approximately 107.65 mM(-1)·s(-1). The maximum temperature of NPs solution could reach to 57.8℃ after continuous near infrared laser irradiation. The transmission electron microscopy imaging revealed that the NPs could target and enter into the endoplasmic reticulum of SK-BR-3 cells. MRI analysis showed the lowest T(2) relaxation time in the tumor sites 24 h after tail vein injection of the NPs. The △T(2) of the tumor sites in the Fe(3)O(4)-trastuzumab-ICG group (30.7±4.8) ms was higher compared with that of control group (3.1±1.1) ms, Fe(3)O(4)-IgG-ICG group (4.4±0.9) ms and trastuzumab + Fe(3)O(4)-trastuzumab-ICG group (11.3±3.8) ms., respectively, all showing statistically significant differences (P<0.05). The fluorescence imaging revealed that the NPs was concentrated transiently in the intraperitoneal organs and tumor sites, then excreted into the bladder. After 24 h, there was an obvious aggregation in the tumor sites. The near infrared thermal imaging experiments showed that the temperature of tumor sites in Fe(3)O(4)-trastuzumab-ICG group could go up to 49.4℃ after continuous near infrared light irradiation. Conclusion: The newly constructed Fe(3)O(4)-trastuzumab-ICG NPs have the potential to act as a multifunctional imaging agent and a powerful tool for photothermal therapy for HER-2 positive breast cancer.

[Study on periodic changes in onset of aortic dissection].

Objective: To investigate theperiodic changes in onset of aortic dissection. Methods: The clinical data of 1 121 patients with acute aortic dissection from Hebei province, treated at Fuwai hospital from January 1, 2010 to December 31, 2016, were collected and analyzed retrospectively. The regularity for the onset of aortic dissection was analyzed according to daytime (1:00 to 6:00, 7:00 to 12:00, 13:00 to 18:00, and 19:00 to 24:00), weekday, month, and quarter. Meanwhile,the differences in various type of aortic dissection patient were also compared. Results: The patients were (51.4±12.0) years old,77.88% (873 cases)were male and 69.05% (774 cases) were type A aortic dissection.The peak period for the onset of the disease in a day was from 13:00 to 18:00 (401 cases. 35.77%),and disease onset was less frequent from 1:00 to 6:00 (196 cases, 17.48%).The peak weekday of disease onset was Monday (173 cases, 15.43%) , and disease onset was less frequent on Friday (153 cases, 13.65%) . The peak month of disease onset was January (135 cases, 12.04%), and disease onset was less frequent in July(54 cases, 4.82%). The peak season of disease onset was winter (349 cases, 31.13%), and disease onset was less frequent in summer (184 cases, 16.41%). Number of disease onset was similar between ≥65 years old and<65 years old groups, with or without hypertension groups, with or without Marfan syndrome groups at different periods of a day, each weekday, and seasons(all P>0.05). Conclusion: There are periodic changes in the onset of acute aortic dissection,which is higher in winter than in summer, higher in the afternoon than in the morning.

[Correlation between of aortic dissection onset and climate change].

Objective: To explore the relationship between the incidence of aortic dissection and climate change. Methods: The characteristics of 345 acute aortic dissection patients came from Beijing in Department of Vascular Surgery, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College from January 2005 to December 2015 were analyzed, retrospectively. There were 266 male and 79 female patients with a mean age of (49±12) years. There were 209 cases of Stanford type A aortic dissection, and 136 cases of type B. According to Fuwai aortic dissection classification: type A 8 cases, type B 95 cases, type Cp 13 cases, type Ct 187 cases, type Cd 40 cases, type D 2 cases. Meanwhile, monthly maximum temperature, minimum temperature, average temperature, average pressure, amount of rainfall, sunshine, relative humidity and other meteorological data were collected. Rank-sum test was used to analyze the difference of onset of aortic dissection in different seasons and months. Generalized additive models were implied to explore climate change and the onset of aortic dissection. Results: The onset of aortic dissection was related to season. Winter had higher morbidity compared to summer (M(Q(R)): 3(2) vs. 2(2), Z=1.97, P=0.05). The occurrence of aortic dissection was associated with month.December had the largest quantity, July had the least (2(3) vs. 2(1), Z=2.42, P=0.02). The mean temperature was statistically significant for indicating the change of aortic dissection onset. It meaned that onset probability was increased with the decrease of temperature (RR=1.01, 95%CI: 1.00 to 1.02, P=0.04). Conclusions: The onset of aortic dissection had something to do with season and month. The incidence of aortic dissection increases with temperature decreases.

[Application of the descending branch of the lateral circumflex femoral artery in the coronary artery bypass grafting operation].

Objective: To investigate the technical method for harvesting and application of the descending branch of the lateral circumflex femoral artery (DBLCFA) in the coronary artery bypass grafting (CABG) operation. Methods: Between December 2016 and April 2017, 19 patients were arranged to use DBLCFA and got CT angiography (CTA) of pelvic and femoral arteries pre-operative at Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Finally, DBLCFA was harvested in 16 patients (including 2 female patients, with a mean age of (47.4±8.5) years) through the anterior thigh incision (13 cases on the left side, 3 cases on the right side). The CABG operations were performed under the cardiopulmonary bypass support (in 10 cases) or under the beating heart condition (in 6 cases), and the DBLCFA conduit was used combining with bilateral internal thoracic artery (in 12 cases), radial artery (in 7 cases) and saphenpous vein (in 3 cases). Results: Due to anatomical variations such as short length and anomalous branch, or due to silent atherosclerosis stenosis of femoral artery, DBLCFA in 3 patients was considered inappropriate for use and was not harvested after CTA examination. In another 16 patients, DBLCFA was safely and quickly harvested and successfully used. On average, 3.4±0.6 anastomosis was built up in CBAG, no adverse effects were exhibited. The length of the harvested DBLCFA was (10.3±1.8) cm, with average lumen diameter of (1.9±0.5) mm. DBLCFA was used as free graft in 15 patients (7 to the first diagonal branch, 6 to the ramus intermedius branch, 1 to the left anterior descending branch and 1 to the second obtuse marginal branch). In 1 patient, the DBLCFA was firstly implanted end-to-side to the internal thoracic artery as a "Y" type composite graft, and then anastomosed to the third obtuse marginal branch. Conclusions: The descending branch of the lateral circumflex femoral artery is an option conduit in CABG. It can be harvested easily and safely. However, pre-operative CTA examination is necessary to exclude the variation and appropriate strategy for graft establishment should be considered during the operation.

Research of the relationship between ß-catenin and c-myc-mediated Wnt pathway and laterally spreading tumors occurrence.

OBJECTIVE: We studied the relationship between the occurrence of laterally spreading tumors (LSTs) and the activation of Wnt/ß-catenin/c-myc pathway. PATIENTS AND METHODS: 20 cases of colorectal polypoid adenomas (PAs) tissue sample, 20 cases of LSTs tissue sample and 20 cases of colorectal cancer tissue sample were acquired, and positive expression of Wnt/ß-catenin/c-myc proteins were detected by immunohistochemical staining. In addition, relative expression levels of mRNA and protein were measured using RT-PCR and Western blotting method. RESULTS: The positive expression levels of Wnt/ß-catenin/c-myc protein in the colorectal cancer group were higher than that in LST group, and the value of the PAs group was the lowest; differences were statistically significant (p < 0.05). The relative expression levels of Wnt/ß-catenin/c-myc mRNA and protein in colorectal cancer group were higher than that in LST group, and the value of PAs group was the lowest; differences were statistically significant (p < 0.05). CONCLUSIONS: The activation level of the Wnt/ß-catenin/c-myc pathway has a close relation to the occurrence and deterioration of LSTs.

[Analysis of the effect of mesial implant position on surrounding bone stress of mandibular edentulous jaw under dynamic loads].

Objective: To evaluate the effect of different placement of mesial implants in edentulous jaws on the stress of the implant and the surrounding bone tissue by three-dimensional (3D)finite element analysis. Methods: Cone-beam CT data of mandibular edentulous patients was transferred into Mimics 17.0 and UG NX8.5 software, and three groups of 3D solid model were established: two mesial implants were implanted in the anterior region of the mandible (bilateral central incisor, lateral incisor, canine), and two distal oblique implant with 30° were implanted in the mandibular second premolar area(5 mm near the mental foramen). Set mandible 3D model with 4 implant by using UG NX8.5 software, produced 3 groups (mandible Ⅰ-Ⅲ). We took dynamic loading on models with help of software Abaqus 6.12, working side posterior teeth loading was set to 150 N and the simulation cycle was 0.875 s. The first stage: 0.000 s to 0.130 s, the lower jaw moves outward (moving toward the side of the work), with no contact between the upper and lower teeth; the second stage: 0.130 s to 0.150 s, mandibular upward, the same tooth tip of the working side were relative, the loading position were the posterior buccal tip, tongue tip; the third stage: 0.150 s to 0.260 s, the buccal slopes of buccal tips of mandibular posterior teeth glide along the lingual slopes of buccal tips of maxillary posterior teeth, the loading force was from the buccal side to the lingual side, the long axis of the tooth was 45°, loaded on the buccal slopes of buccal tips of posterior teeth; the fourth stage: 0.260 s to 0.300 s, the lingual slopes of buccal tips of mandibular posterior teeth glide along the buccal slopes of the tongue tips of maxillary posterior teeth, separate from the tip of the tooth at half the length, the loading force was from the lingual side to the buccal side, the long axis of the tooth was 45°, loaded on the lingual slopes of buccal tips of posterior teeth; the fifth stage: 0.300 s to 0.875 s, at the unloading stage, mandibular posterior teeth were separated from the maxillary teeth and returned to the intercuspal position. The loading position varied according to the mastication cycle. The stress distribution of implant and surrounding bone tissue at different stages of each model were observed. Results: From the early stage to chew occlusal contact to the end of the mastication cycle, three groups of models were displayed: the stress of distal implants was greater than that of mesial implants and the neck stress reached the maximum and gradually decreased to the root tip. The stress of distal implant bone was greater than that of mesial implant bone and the stress of distal bone of distal implant was greater than that of mesial bone of distal implant. All the stress peak showed a gradual increase, and the stress reach the maximum at the fourth stage. In the 3 models, the bone stress around the distal implant of model of the anterior implant located in the lateral incisor region was the lowest. The peak stress of cortical bone of the distal position of implant was 58.7 MPa. The bone stress around the distal implant of model of the anterior implant located in the canine region reached the maximum, and the peak stress of cortical bone of the distal position of implant was 135.6 MPa. Conclusions: When mesial implants of edentulous jaws located in the lateral incisor region, it is good for stress dispersion.

[Preliminary application of amide proton transfer imaging signal in acute ischemic stroke].

OBJECTIVE: To apply amide proton transfer magnetic resonance imaging (APT-MRI) technique to acute ischemic stroke, and to discuss clinical values of the APT-MRI main parameter - MTRasym(3.5 ppm). METHODS: A total of 18 emergency admitted patients, with acute ischemic stroke from Beijing Hospital, were recruited from March to November 2015. Eventually, 18 patients (male 14, female 4, average age 72 years old, age ranged from 52 to 92 years, symptom onset ≤24 hours, 2 patients≤ 6 hours) were included in this study. All patients underwent MR scanning on the brain at 3.0 Tesla. Besides the conventional scans for stroke, the APT sequence (saturation time 0.8 s, saturation power 2 µT) was performed. APT weighted (APTW) images were calculated using magnetization transfer ratio asymmetry at 3.5 ppm with respect to water. MRI signals in APTW, diffusion weighted images (DWI) and fluid attenuated iversion recovery (FLAIR) were visually evaluated. Shapiro-Wilk tests were performed to find out the distribution of MTRasym(3.5 ppm) in the whole sample, infarction regions, and normal appearing white matter (NAWMs), respectively. Detrended normal P-P plots were also used to evaluate its normality. Paired-t test and two-sample t test were applied to compare the mean MTRasym(3.5 ppm) of infarction regions with that of contra lateral NAWMs. RESULTS: (1) High signal intensity was observed in DWI and FLAIR in all 18 patients. However, signal intensity was somewhat different in APTW. 13 patients were found decreased APT effect, and 5 patients were with equal APT effect in infarction regions. In NAWMs, 14 patients were found equal APT effect, and 4 patients were with decreased APT effect. (2) MTRasym(3.5 ppm)s were proven, with Shapiro-Wilk test, to distribute normally within the whole sample (W=0.964, P=0.288), infarction regions (W=0.962, P=0.645), and NAWMs(W=0.929, P=0.187). However, its normality was not so satisfactory due to greater deviations (absolute value>0.06) of some cases in detrended normal P-P plots. (3) Paired-t test analysis showed that MTRasym(3.5 ppm) in infarction regions (-0.035%±1.020%) was significantly lower than that in NAWMs (0.386%±0.790%) (t=-2.273, P=0.036). However, there was no statistically significant difference between infarction regions and NAWMs when two sample t-test was performed (t=-1.386, P=0.175). CONCLUSION: MTRasym(3.5 ppm) can be used to evaluate acute ischemic stroke with a broad future scope in clinical.

Comparison of the treatment effects of methoxamine and combining methoxamine with atropine infusion to maintain blood pressure during spinal anesthesia for cesarean delivery: a double blind randomized trial.

OBJECTIVE: Hypotension is a common complication of spinal anesthesia for cesarean delivery. Atropine is a vagus nerve blocker that can antagonize vagus excitation to mitigate the reflex bradycardia. We aimed to assess the effect of methoxamine-atropine therapy in treating spinal anesthesia hypotension for cesarean section. PATIENTS AND METHODS: This is a double-blind randomized controlled study. Women under spinal anesthesia for elective caesarean delivery received boluses of methoxamine 2 mg alone (Group M, n = 40), or with addition of atropine 0.1 mg (Group MA1, n = 40), atropine 0.2 mg (Group MA2, n = 40) or atropine 0.3 mg (Group MA3, n = 40) upon a maternal systolic pressure ≤ 80% of baseline. The primary endpoint was systolic blood pressure and the secondary endpoints were maternal heart rates, instant neonatal heart rates, umbilical artery pH and umbilical artery base excess. RESULTS: Changes in systolic blood pressure were similar among the four groups. The incidences of bradycardia in groups M and MA1 were significantly higher than those in group MA2 and MA3. The fetal heart rates after delivery in groups MA2 and MA3 were higher than those in group M and MA1 but within the normal range. The acid-base status had no difference in the four groups. CONCLUSIONS: Methoxamine-atropine combination has a similar efficacy to methoxamine alone but has an increased hemodynamic stability and a less adverse effect occurrence.

Effect of mannitol injection by intravenous catheter on ear vein endothelial cell apoptosis and venous thrombus in rabbits.

OBJECTIVE: To evaluate the effect of mannitol injection into the rabbit ear vein by intravenous catheter on endothelial cells apoptosis, thrombus formation, the expression of plasma tissue factor (TF) and von Willebrand factor (vWF). MATERIALS AND METHODS: Sixty-four Zealand rabbits were randomly divided into experiment and control group and received 20% mannitol or normal saline via ear margin veins, respectively. Both groups were injected daily. On days 1, 3, 5, and 7 after catheterization, rabbits were subjected to intraperitoneal anesthesia and their ear veins were isolated and then subjected to hematoxylin and eosin staining. Cell apoptosis was evaluated using TUNEL (terminal deoxynucleotide transferase mediated d-UTP nick end labeling) staining, and the levels of TF and vWF were analyzed by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the experiment group showed significantly increased thrombus formation (p < 0.05), and a significant higher rate of apoptosis in endothelial cells (p < 0.05) on days 3, 5, and 7. In addition, the experiment group showed significant elevation of plasma TF and vWF on days 3, 5, and 7 (p < 0.05). CONCLUSIONS: Continuous mannitol injection by intravenous catheterization induces more serious venous thrombus formation and endothelial cells apoptosis and higher TF and vWF levels than normal saline injection. These data suggest that clinical use of hyperosmotic mannitol by intravenous catheter may exert direct deleterious effects on vascular endothelium.

Optical and magneto-optical anisotropies in large-area two-dimensional Co antidots film.

In this work, we investigate the plasmon-induced optical and magneto-optical anisotropies in the large-area square-ordered Co antidots film. It shows that both the outline of reflectivity spectrum and Kerr spectrum are significantly modified by surface plasmon polarition (SPP) resonances. Moreover, the magnitude of Kerr angle reaches to about 10 minutes at the azimuthal angle 45°, which is over 3 times of that of pure Co film. These phenomena are attributed to the SPP resonances with different diffraction orders of reciprocal lattice vectors.

Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene.

Genes that are differentially expressed between schizophrenia patients and healthy controls may have key roles in the pathogenesis of schizophrenia. We analyzed two large-scale genome-wide expression studies, which examined changes in gene expression in schizophrenia patients and their matched controls. We found calcium/calmodulin (CAM)-dependent protein kinase kinase 2 (CAMKK2) is significantly downregulated in individuals with schizophrenia in both studies. To seek the potential genetic variants that may regulate the expression of CAMKK2, we investigated the association between single-nucleotide polymorphisms (SNPs) within CAMKK2 and the expression level of CAMKK2. We found one SNP, rs1063843, which is located in intron 17 of CAMKK2, is strongly associated with the expression level of CAMKK2 in human brains (P=1.1 × 10(-6)) and lymphoblastoid cell lines (the lowest P=8.4 × 10(-6)). We further investigated the association between rs1063843 and schizophrenia in multiple independent populations (a total of 130 623 subjects) and found rs1063843 is significantly associated with schizophrenia (P=5.17 × 10(-5)). Interestingly, we found the T allele of rs1063843, which is associated with lower expression level of CAMKK2, has a higher frequency in individuals with schizophrenia in all of the tested samples, suggesting rs1063843 may be a causal variant. We also found that rs1063843 is associated with cognitive function and personality in humans. In addition, protein-protein interaction (PPI) analysis revealed that CAMKK2 participates in a highly interconnected PPI network formed by top schizophrenia genes, which further supports the potential role of CAMKK2 in the pathogenesis of schizophrenia. Taken together, these converging lines of evidence strongly suggest that CAMKK2 may have pivotal roles in schizophrenia susceptibility.

Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.

Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10(-5), odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations.

Resection with total caudate lobectomy confers survival benefit in hilar cholangiocarcinoma of Bismuth type III and IV.

PURPOSE: To identify prognostic predictors for overall survival of patients with hilar cholangiocarcinoma of Bismuth type III and IV (HCBT34), and to determine survival benefit and safety of total caudate lobectomy (TCL) in a Chinese centre. METHODS: From January 2001 to December 2010, 171 patients with the diagnosis of HCBT34, who underwent a potentially curative resection, were included in this study. Cox proportional hazards regression models were used to determine the association between possible prognostic variables and survival time. Curative resectability rate, morbidity and mortality were investigated also. RESULTS: Resection with TCL was significantly associated with more opportunity to achieve curative resection (p < 0.01), did not accompany with more morbidity (p = 0.39) and mortality (p = 0.67). Cox regression analysis demonstrated positive resection margins [Relative Risk (RR) 3.6, 95% CI 3.5-3.7], not well differentiation (RR 2.9, 95% CI 2.7-3.1), higher preoperative serum peak CA19-9 level (RR 1.6, 95% CI 1.5-1.7) and regional lymph nodes involvement (RR 1.5, 95% CI 1.4-1.6) as independent adverse prognostic variables. CONCLUSIONS: Resection with TCL offers a long-term survival opportunity for HCBT34, with high curative resectability rates and an acceptable safety profile.

Inhibition of the acquisition of conditioned place aversion by dopaminergic lesions of the central nucleus of the amygdala in morphine-treated rats.

The negative affective state of opiate abstinence plays an important role in craving and relapse to compulsive drug use. The dopamine system participates in the reward effects of opiate use and the aversive effect of opiate abstinence. The amygdala is an essential neural substrate for associative learning of emotion. To establish a model of conditioned place aversion (CPA) in morphine-treated rats, we used different visual and tactual cues as conditioned stimuli (CS) within a conditioning apparatus. An injection of naloxone served as the unconditioned stimulus (US). The 6-hydroxydopamine (6-OHDA) lesion technique was used to investigate the effects of the dopaminergic system of the central nucleus of the amygdala (CeA) on naloxone-induced CPA. Rats were rendered physically dependent via administration of increasing doses of morphine delivered via intraperitoneal injection. Doses increased by 20 % each day for 14 days, starting from an initial dose of 6 mg/kg. All rats also received a low dose of naloxone (0.1 mg/kg) by injection 4 hours after morphine treatment on days 11 and 13 to induce CPA in a biased two-compartment conditioned place apparatus. Morphine-dependent rats with sham lesions were found to develop significant CPA after naloxone treatment. Bilateral 6-OHDA lesions of the CeA impaired the acquisition of CPA but had no effect on locomotor activity. These results suggest that the dopaminergic system of the CeA plays an important role in the negative affective state of opiate abstinence.

Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese.

BACKGROUND: Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. Several lines of linkage and association studies have repeatedly suggested that the chromosome 5q22-33 region is implicated in the aetiology of schizophrenia. However, most of the previous studies on the linkage of 5q22-33 with schizophrenia were from European populations, and it was not well characterised in other populations. METHODS: We analysed eight single nucleotide polymorphisms (SNPs) located in the 5q23.3 region in a cohort of 506 schizophrenia patients and 672 control subjects from south western China. Single marker association, haplotypic association, sex-specific association and molecular evolutionary analysis were performed. RESULTS: Single marker analysis indicated that SNP5 (rs1355095) in LOC728637 is associated with schizophrenia. When males and females were analysed separately, SNP4 (rs31251) in PDZ-GEF2 is associated with schizophrenia in females. Further analysis using haplotypes demonstrated that a haplotype block spanning PDZ-GEF2, LOC728637 and ACSL6 is highly associated with schizophrenia and several haplotypes in this haploblock have about twofold to 10-fold increase in the affected subjects. In addition, molecular evolutionary analysis suggests that PDZ-GEF2 has undergone adaptive evolution due to Darwinian positive selection in the human lineage. CONCLUSION: Our data provide evidence of the association of 5q22-33 with schizophrenia in Han Chinese. This chromosomal region is likely responsible for genetic susceptibility to schizophrenia, supporting previous data from European patients. In addition, our evolutionary analysis is consistent with the hypothesis that genes contributing to schizophrenia are likely under positive selection during human evolution.

A modified cannulating technique for the BVS5000.

The aim of this study was to report on a modified cannulating method for the BVS5000 left ventricular assist device. From April 2005 to April 2006, a BVS5000 device was implanted using a modified cannulating method in 7 postcardiotomy male patients after coronary artery bypass grafting for left ventricular support. The inflow cannula was inserted into the left atrial artery through a segment of bovine jugular vein and the arterial cannula into the femoral artery. Five patients were successfully weaned from the BVS5000 after recovery of heart function and were discharged from hospital. The BVS5000 was explanted using a minimally invasive technique. The weaning procedure was completed bedside in the intensive care unit under local anesthesia; resternotomy was not necessary. The modified technique is a simpler, safer and more minimally invasive method for selected patients supported by the BVS5000.