Magnetic resonance imaging assessment of substantia nigral iron deposition in Parkinson's disease: a meta-analysis.

OBJECTIVE: The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. MATERIALS AND METHODS: Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. RESULTS: We included 16 studies with sample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). CONCLUSIONS: Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed.

[Application value of questionnaires in the screening obstructive sleep apnea syndrome in pregnancy across trimesters].

Objective: To evaluate the clinical utility value of questionnaires of Berlin, STOP, STOP-Bang (SBQ), Epworth Sleepiness Scale (ESS) in screening obstructive sleep apnea syndrome (OSAS) in pregnant women of different trimesters. Methods: Consecutive pregnant women at high risk for OSAS were enrolled from January, 2021 to April, 2022 at the obstetric clinic of Peking University People's Hospital. They completed questionnaires of Berlin, STOP, SBQ, ESS and also underwent an overnight polysomnography (PSG). To evaluate the accuracy of questionnaires of Berlin, STOP, SBQ, ESS, sensitivity, specificity, positive predictive values, negative predictive values and the area under the receiver operating characteristics (ROC) curve of these questionnaires in pregnancy across trimesters (Pregnancy 1-15 weeks was the first stage, pregnancy 16-27 weeks was the second stage, and pregnancy 28-40 weeks was the third stage) were calculated. Results: A total of 100 pregnant women [(34.5±4.3) years old (26-46 years old)] were included in this study, including 20, 35 and 45 pregnant women in the first, second and third trimester of pregnancy, respectively. Based on PSG results, 45 (45%) of 100 pregnant women were diagnosed with OSAS. The overall predictive values of the four questionnaires were not good, area under[AUC(95%CI)] the ROC curve ESS, Berlin questionnaire STOP and SBQ were 0.54(0.43, 0.66), 0.59 (0.47, 0.70), 0.62(0.51, 0.73) and 0.61 (0.49, 0.72), respectively, sensitivity was 35.6%, 65.9%, 48.9%, 28.9%, specificity was 71.7%, 52.5%, 73.6%, 92.5%. When categorized according to trimesters, the predicted values of the four questionnaires increased in the first trimester, the AUC (95%CI) of STOP questionnaire was 0.81 (0.61, 1.00), sensitivity was 75.0%, specificity was 87.5%. Conclusion: The overall predictive power of the four screening questionnaires is limited in pregnant women. But predictive value of STOP questionnaire is acceptable in the first trimester.

[Clinical outcomes analysis of fertility-preserving therapy for atypical endometrial hyperplasia and early endometrial carcinoma].

Objective: To analyze the clinical efficacy of fertility-preserving therapy in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC). Methods: The general condition, pathological type, treatment plan, tumor outcomes and pregnancy outcomes of 110 patients with AEH and EC treated with fertility-preserving therapy in Peking University People's Hospital from December 2005 to September 2019 were retrospectively analyzed. Kaplan-Meier and Log rank tests were used for survival analysis. Results: The response rate of 110 cases of AEH (62 cases) and EC (48 cases) was 94.5% (104/110) after fertility-preserving therapy. There were 93 cases (84.5%) achieved complete response and 11 cases (10.0%) achieved partial response, and the recurrence rate was 29.0% (27/93). The complete response rates of AEH and EC were 90.3% (56/62) and 77.1% (37/48), respectively, without significant difference (P=0.057). The recurrence rates of EC were significantly higher than that of AEH (40.5% vs 21.4%; P=0.022). Forty-one patients with complete response had pregnancy intention, the pregnancy rate was 70.7% (29/41), and the live birth rate was 56.1% (23/41). The live birth rate of AEH was 68.2% (15/22) and that of EC was 42.1% (8/19), the difference was statistically significant (P=0.032). The pathological type was related with the recurrence (P=0.044). Conclusions: Patients with AEH and EC can obtain high complete response rate and pregnancy rate after fertility-preserving therapy. The recurrence rate of EC is higher than that of AEH, while the live birth rate of AEH is higher than that of EC.

[Analysis of prognosis and pregnancy outcomes of fertility-preserving treatment for patients with stage â a, grade 2 endometrial cancer].

Objective: To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC). Methods: Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G(1), G(2) or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G(2) EC group, G(1) EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results: (1) Totally 57 eligible patients were included in this study, including 11 cases with G(2) EC, 22 cases with G(1) EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G(2) EC, G(1) EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P>0.05). Median remission time was significantly longer in the G(2) EC group than those in the other two groups (8, 6 and 4 months; P=0.046). Among 9 G(2) EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference (P>0.05). However, time interval to pregnancy was shorter in G(2) EC patientsthan the other two groups (4, 9 and 22 months, respectively; P=0.006). Conclusions: Fertility-preserving treatment for patients with stageⅠa, G(2) endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.

[A survey on clinical characteristics and risk factors of severe asthma in China].

Objective: To investigate the clinical characteristics and risk factors of severe bronchial asthma in Chinese people over 14 years old. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) located in seven regions (north, northeast, east, central China, south, southwest and northwest) of China from February 2010 to August 2012. A total of 2 034 were diagnosed as asthma. The clinical characteristics and related risk factors of patients with severe asthma in China were analyzed. Results: Among all asthma patients, 560 were newly diagnosed, accounting for 27.5% (560/2 034) and the percentage of previously confirmed patients was 72.5% (1 474/2 034). A total of 145 were eligible for severe asthma, accounting for 9.8% (145/1 474) of previously confirmed asthmatics and 7.1% (145/2 034) of all asthmatics. 83.5% (121/145) severe asthmatics had at least one trigger factor. Correlation analysis showed that the risk factors of severe asthma were: smoking (OR=1.543, 95%CI: 1.250-1.814), obesity (OR=2.186, 95%CI: 1.972-2.354), petting (OR=2.135, 95%CI: 1.904-2.283), combined with allergic rhinitis (OR=3.456, 95%CI: 2.721-4.326), gastroesophageal reflux disease (OR=1.842, 95%CI: 1.682-2.140), bronchiectasis (OR=1.665, 95%CI: 1.347-1.912) or chronic obstructive pulmonary disease (OR=1.312, 95%CI: 1.171-1.694). Conclusions: The most common comorbidities in severe asthmatics in China are allergic rhinitis and gastroesophageal reflux disease. The risk factors of severe asthma include obesity, allergic rhinitis, gastroesophageal reflux disease, chronic obstructive pulmonary disease, bronchiectasis, smoking and petting.

miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN.

Thyroid cancer is one common endocrine malignancy with various pathological types. MicroRNAs (miRNAs) play essential roles in development, prognosis and treatment of thyroid cancer. However, the role of miR-17-5p in thyroid cancer progression and its mechanism remain poorly understood. The expressions of miR-17-5p and phosphatase and tensin homolog (PTEN) were measured in thyroid cancer tissues and cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. The protein levels of biomarkers in autophagy or protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway were analyzed by western blot. The interaction between miR-17-5p and PTEN was probed by luciferase activity assay. We found that miR-17-5p expression was elevated and PTEN level was reduced in thyroid cancer tissues and cells compared with their corresponding controls. Knockdown of miR-17-5p or overexpression of PTEN suppressed cell proliferation and autophagy but promoted apoptosis in thyroid cancer cells. PTEN was indicated as a target of miR-17-5p and its interference reversed abrogation of miR-17-5p-mediated inhibition of proliferation and autophagy and increase of apoptosis. Moreover, downregulation of miR-17-5p impeded the activation of AKT/mTOR pathway in thyroid cancer cells, which was attenuated by silencing PTEN. Our data supported that knockdown of miR-17-5p upregulated PTEN expression, therefore leading to suppression of the malignancy of thyroid cancer and inactivation of AKT/mTOR pathway, providing a novel avenue for treatment of thyroid cancer.

Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients.

OBJECTIVE: The ubiquitin-conjugating enzyme E2C (UBE2C) has been known as a crucial factor upregulated in various tumors. The functions of UBE2C is mainly involved in the pathway protein ubiquitination. This study investigates the expression of UBE2C in gastric cancers and its correlation with overall survival rate. MATERIALS AND METHODS: Real-time PCR (RT-PCR) and Western blotting were performed to determine the expression of UBE2C in gastric cancer samples and adjacent normal tissues. Immunohistochemical staining was used to assess the expression of UBE2C in 216 paraffin-embedded gastric cancer tissues. RESULTS: The mRNA and relevant protein levels of UBE2C in gastric cancer tissues are significantly greater than those in the adjacent normal tissues. Also, the expression of UBE2C is found to correlate with lymphatic metastasis, serosa invasion, TNM (Malignant Tumors) staging and Lauren's classification (p<0.05). The univariate analysis shows that the overexpression of UBE2C associates with poor prognosis (p=0.001). The multivariate analysis demonstrates that expression of UBE2C, lymphatic metastasis, and TNM staging are independent prognostic indicators. CONCLUSIONS: This study shows that overexpression of UBE2C contributes to the development of gastric cancer, and UBE2C has the potential to be exploited as a therapeutic target.

[The relationship between smoking status and epidermiology of asthma in people aged over 14 years in China].

Objective: To study the relationship between bronchial asthma and smoking status in Chinese people. Methods: Asthma epidemiological survey and stratified-cluster-random method survey were performed in residents over 14 years in 8 provinces (cities) of China from February 2010 to August 2012. Asthma was diagnosed based upon case history, clinical signs and lung function test. Smoking status was investigated by questionnaire. Results: Sampling population was 180 099 and 164 215 were valid. A total of 2 034 subjects were diagnosed as asthma including 79 692 men and 84 523 women. The overall prevalence rate of asthma was 1.24% (2 034/164 215). Smokers were 23.8% (39 137/164 215) in the whole population. Smokers were 34.5% (702/2 034) in asthmatic patients, compared with 23.7% (38 435/162 181) in no-asthmatic population. The incidence of asthma was 1.79% and 1.06% in smokers and non-smokers respectively (P<0.001), suggesting that OR of smoking was 1.70 (95% CI 1.55-1.86, P<0.001). According to asthma control test (ACT) score, the level of asthma control in non smoking group was higher than that in smoking group(43.2% vs 35.3%). The times of hospitalization due to acute exacerbations(0.51 vs 0.41 events/person/year), total hospitalization rate(27.35% vs 20.12%), annual emergency room visits (0.80 vs 0.60 events/person/year) and emergency room visit rate (31.77% vs 24.47%) were all much higher in smoking asthmatic patients than those in non smoking asthmatic patients, indicating that the level of asthma control in smoking patients was significantly worse than in non smoking patients. Conclusions: The smoking rate in Chinese people over 14 years is still high. The prevalence rate of asthma in smokers is significantly higher than that of non-smokers. The level of asthma control in smokers is significantly worse than that in non smokers.

The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis.

Juvenile amyotrophic lateral sclerosis (JALS) occurs at an age of onset below 25 years with a heterogeneous disease onset location, variable progression and survival time. To investigate whether an ALS gene profile could resolve any aspects of clinical symptom heterogeneity, we have used targeted sequencing technology in a cohort of 12 JALS patients of Chinese descent. We detected 5 likely pathogenic mutations, 2 in familial probands and 3 in sporadic patients. One was a known TARDBP mutation (p.G348V) and 4 were FUS frameshift mutations including a known p.Gln519Ilefs*9 mutation and 3 novel mutations, p.Gly515Valfs*14, p.Gly486Profs*30, and p.Arg498Alafs*32. Of the 4 FUS mutations, 2 were able to be confirmed as de novo mutations. The TARDBP mutation carrier showed a classic ALS phenotype. All patients with FUS mutations experienced limb weakness at an early age and developed bulbar symptoms during the disease course. FUS mutations have previously been associated with increased JALS disease progression, however, we found a large range 12 to 84 months in disease survival (mean 58.2 months). Our results justify future screening for variants in FUS as it remains the most frequent genetic determinant of early onset, JALS (found in 30% of our patients).

[A trend analysis of the incidence of occupational diseases in Chongqing, China, from 2006 to 2014].

Objective: To investigate the incidence of occupational diseases in Chongqing, China, from 2006 to 2014, and to analyze the harm, features, and trend of occupational diseases in Chongqing. Methods: The data of new cases of occupational diseases from 2006 to 2014 were collected, and the patients with a confirmed diagnosis of occupational diseases were selected as study subjects to analyze the incidence of occupational diseases in Chongqing. Results: There were 17499 cases of occupational diseases in total in Chongqing from 2006 to 2014. Among these patients, 17124 (97.86%) were male, most of whom (95.40%) had occupational pneumoconiosis, and 375 (2.14%) were female, most of whom (72.80%) had occupational chemical poisoning. There were 16400 cases (93.72%) of occupational pneumoconiosis in total, mainly coal workers' pneumoconiosis (55.87%) and silicosis (43.02%) , and the main industries involved were coal mining and washing, railway transport equipment manufacturing, and mining and washing of bituminous coal and anthracite. There were 724 cases of occupational poisoning in total; there were 281 cases of acute occupational poisoning, mainly gas poisoning (39.86%) and carbon monoxide poisoning (33.10%) ; there were 443 cases of chronic occupational poisoning, mainly poisoning caused by benzene (47.63%) , mercury and its inorganic compounds (32.74%) , and lead and its inorganic compounds (9.03%) . Conclusion: Occupational diseases in Chongqing are mainly occupational pneumoconiosis, and occupational health supervision should be enhanced in the industries of coal mining and washing and railway transport equipment manufacturing to protect workers' health.

Inadvertent intrathecal injections and best practice management.

The intrathecal space has become an important anatomic site for medical intervention not only in anesthesia practice, but also in many other medical specialties. Undesired/inadvertent intrathecal injections (UII) are generally rare. There is tremendous variation in reported inadvertent administrations via an intrathecal route in the literature, mainly as individual cases and very small case-series reports. This review aims to identify potential sources of UII, its clinical presentations, and appropriate management. The inadvertent injectants are classified as anesthetic agents and pain medicines, chemotherapeutics, radiological contrast agents, antibiotics and corticosteroids, and miscellaneous chemical agents such as tranexamic acid. The clinical effects of UII are dependent upon inadvertent injectant(s) and dose being administered intrathecally, and can range from no adverse effect to profound neurological consequences and/or death. Prompt cerebrospinal fluid (CSF) lavage and cardiopulmonary support seem to be the mainstay of treatment. If serious consequences are anticipated, CSF lavage could be lifesaving. This review additionally provides some options for comprehensive management and preventing strategies.

[A cross-section study of severe asthma in eight provinces of China].

Objective: To analyze the prevalence of severe asthmain China. Methods: The epidemiological data was collected from 2 034 asthmatics who were diagnosed in the last epidemiological survey from 2009 to 2010 in 8 provinces. Results: According to the questionnaire survey, among the 2 034 patients, the previously diagnosed patients accounted for 72.47% (1 474/2 034) and the percentage of newly-diagnosed patients was 27.53% (560/2 034). In those 1 474 previously diagnosed asthmatics, 122 (8.28%) were classified into severe asthma, while 6.00% (122/2 034) of all asthmatics and 0.07% (122/164 215) of total respondents presented as severe cases. Statistically, there was no difference in the prevalence of severe patients between men and women. The morbidity rate of severe asthma was the lowest in the 21-30 year old group and the highest in 61-70 year old group (0.85% and 8.31% respectively). The difference among ages was statistically significant (χ2=18.791, P=0.005). In addition, the prevalence rates of severe asthma were also significantly diverged among patients with different education background(χ2=24.639, P<0.000 1). A negative relation was found between education level and the proportion of severe cases. Moreover, the morbidity of severe asthma in smoking patients and non-smoking patients were significantly different as well (χ2=7.447, P<0.05). Compared with asthma patients who do not smoke, smokers were more likely to suffer severe asthma (OR=1.663, 95% CI 1.150-2.404). Conclusions: The prevalence rate of severe asthma in China is similar to that in other countries.Elderly patients have higher risk of severe asthma. Smoking is considered as a risk factor for severe asthma.

Mucormycosis or extranodal natural killer/T cell lymphoma, similar symptoms but different diagnosis.

Facial mucormycosis and extranodal natural killer/T cell lymphoma (NK/TCL) are characterized by facial progressive swelling, ulceration and destruction. Patient one was a 58-year-old woman, who had typical clinical-pathological symptoms of tumor. She was hospitalized in order to remove the tumor. But the diagnosis turned out to be primary mucor infection, which was corrected by positive tissue culture and fungal elements in histology. She was also diagnosed with type 2 diabetes mellitus and acute myelocytic leukemia M2a. With the antifungal therapy, her symptoms, signs and general conditions improved. Regrettably, she gave up the treatment, and died three months later for unknown reason. Patient two was a 60-year-old woman, with the complaints of chronic sinusitis, swelling and necrotic lesion in the right temporal area. Although the mycelium was recovered in biopsy tissues from the necrotic lesion, the diagnosis was revised to extranodal NK/TCL by reviewing the histopathological features and immunophenotypic analysis. The patient also voluntarily abandoned treatment, and died at home for unknown reason. The differential diagnosis of facial mucormycosis and extranodal NK/TCL is usually perplexing.

[Diagnosis and treatment of pheochromocytoma in pregnancy: a case report].

Pheochromocytoma is rare in pregn'ancy. Clinical features of a case of pheochromocytoma during pregnancy in the Peking University People's Hospital was investigated and the literature reviewed to discuss the diagnosis and treatment of this disease. The patient manifested with hypertension and proteinuria, who was easily misdiagnosed with gestational hypertension disease. When she was transferred to our hospital, the symptoms such as, paroxysmal palpitation, dizziness, vomiting were noticed, and the possibility of pheochromocytoma was considered due to the accompanying abdominal mass. An emergent cesarean section was performed successfully due to preterm labor during the treatment of the disease. After the delivery the drug preparation continued. And the laparoscopic resection of pheochromocytoma proceeded when the blood pressure was steady. The patient recovered fully after the surgery. The final diagnosis of pheochromocytoma was confirmed with the pathology. Its diagnosis and treatment experiences could improve our understanding and treatment of secondary hypertension due to pheochromocytoma in pregnancy.

Bio-Root and Implant-Based Restoration as a Tooth Replacement Alternative.

We previously reported that dental stem cell-mediated bioengineered tooth root (bio-root) regeneration could restore tooth loss in a miniature pig model. As a potential new method for tooth restoration, it is essential to compare this method with the widely used commercial dental implant-based method of tooth restoration. Tooth loss models were created by extracting mandibular incisors from miniature pigs. Allogeneic periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs) were isolated and cultured. A PDLSC sheet was prepared by adding 20.0 µg/mL vitamin C to the culture medium; in addition, a hydroxyapatite tricalcium phosphate (HA/TCP)/DPSC graft was fabricated and cultured in a 3-dimensional culture system. A total of 46 bio-root implantations and 9 dental implants were inserted, and crown restorations were performed 6 mo after implantation. Histological, radiological, biomechanical, and elemental analyses were used to evaluate and compare tissue-engineered bio-roots and dental implants to the natural tooth roots. After 6 mo, both computed tomography scans and histological examinations showed that root-like structures and dentin-like tissues had formed. Three months after crown restoration, clinical assessments revealed that tooth function was equivalent in the regenerated bio-root and the dental implant. Biomechanical testing showed that the bio-roots were similar to natural tooth roots in compressive strength, modulus of elasticity, and torsional force; however, these properties were significantly higher in the dental implants. Elemental analysis revealed a higher similarity in elemental composition between bio-roots and natural tooth roots than between bio-roots and dental implants. However, the dental implant success rate was 100% (9 of 9) and the bio-root success rate was only 22% (10 of 46). Taken together, we showed that an allogeneic HA/TCP/DPSC/PDLSC sheet could successfully build a bio-root with structure and function similar to the natural tooth root; however, tissue engineering procedures must be optimized further to improve the success rate.

The regulatory effects of autophagy to the CNE2 cells radio-sensitization.

To investigate the effects of autophagy activator and autophagy inhibitor on the CNE2 radiation sensitivity of nasopharyngeal carcinoma cells. RNA interference technology was used to silence the atg5 gene and autophagy inhibition cell model was constructed. Rapamycin and chloroquine were treated respectively on cells with X-ray 5Gy irradiation. Cells' growth status were observed for 8 days and control group was set. The cell viability was detected by MTT assay and colony formation assay, and the cell cycle was analyzed by flow cytometry. Compared with the control group, the survival rate, clone formation rate and the survival rate of the irradiation of the other three groups were significantly lower. (P<0.05) Most cells were detected in the G0/G1 phase in the other three groups except the control group, and cells of the other two periods were less than those in the G0/G1 phase. The autophagy inhibitor or activator and atg5 silencing can be increased by CNE2 radiation therapy, however, the sensitization effect increase of autophagy activator is better than others.

Protective effect of nicotine on the cultured rat basal forebrain neurons damaged by ß-Amyloid (Aß)25-35 protein cytotoxicity.

OBJECTIVE: We sought to investigate the intervention effect of nicotine on ß-amyloid (Aß)25-35 protein cytotoxicity in the rat basal forebrain neurons primary cultures. MATERIALS AND METHODS: For this purpose, freshly isolated rat basal forebrain neurons were cultured for 7 days and then exposed to either Aß(25-35) or the combination of Aß(25-35) and nicotine for 48 hours. The effects of Aß(25-35) and nicotine on neurons morphology, growth status and TrkA expression were evaluated through microscopy, MTT assay, RT-PCR and immunocytochemistry. RESULTS: We found that the exposure of cultured neurons to Aß(25-35) resulted in remarkable morphological changes. The average process number and length as well as the maximum process length of neurons were significantly decreased as compared with those of control. MTT assay showed that Aß(25-35) impaired the growth of neurons. Aß(25-35) also inhibited the expression of TrkA at both mRNA and protein levels. However, the addition of nicotine significantly attenuated these changes, indicating that nicotine could protect the neurons from the cytotoxicity of Aß(25-35). CONCLUSIONS: Nicotine could be useful for the treatment of Alzheimer's disease through its ability to rescue the neurons from Aß(25-35) cytotoxicity and the protective effect involved upregulated expression of TrkA receptors.

Association between metabolic syndrome and vascular endothelium dysfunction in children and adolescents.

We aimed at investigating the association between metabolic syndrome (MS) and vascular endothelial cell dysfunction (ECD) in children and adolescents. Sixty children (30 obese children and 30 children with MS) were included in this retrospective analysis. Thirty healthy subjects were randomly selected as the control group. A series of indices/biomarkers known to be related to MS/ECD were determined using ELISA. Correlations between the variables measured were analyzed. Compared with the control group, PAI-1, vWF, VE-cad, TM, and VEGF were significantly increased in the MS group (P < 0.05). Adolescents in the obese group had significantly increased levels of serum PAI-1, VE-cad, TM, and VEGF as compared with the control group (P < 0.05). Further, vWF in the obese and control groups did not differ significantly (P = 0.556). Our results suggest that ECD is correlated with MS in children and adolescents. Pathophysiological changes of the vascular endothelium may exist in obese children who have yet to develope MS. PAI-1, vWF, VE-cad, TM, and VEGF could be used as biomarkers for predicting ECD. ECD that develops in patients with MS may be associated with obesity, elevated blood lipid, elevated blood glucose, and higher blood pressure.

Phosphorylation of human La protein at Ser 366 by casein kinase II contributes to hepatitis B virus replication and expression in vitro.

Human La protein (hLa) is a multifunctional RNA-binding protein involved in the regulation of hepatitis B virus (HBV) expression. Casein kinase II (CK2), a protein kinase, is known to activate hLa by phosphorylating Ser(366). Tetrabromobenzimidazole (TBBz) has been shown to be a specific inhibitor of CK2 activity, which suggests that TBBz may be useful for reducing HBV gene expression. The aim of our study was to determine whether inhibition of CK2 by TBBz and decreased phosphorylation of hLa Ser(366) (pLa) would reduce HBV gene expression. pLa and total La expression levels were evaluated by immunohistochemistry in human liver tissues with or without HBV infection. HepG2.2.15 cells (an HBV-expressing cell line) were treated with TBBz, and cell viability and pLa levels were evaluated. Knockdown of hLa and CK2 levels by specific siRNA and mutant hLa Ala(366) were utilized to establish the roles of pLa and CK2 in HBV gene expression. HBV DNA replication and HBsAg and HBeAg levels were analysed in HepG2.2.15 cell supernatants by standard methods. pLa was significantly overexpressed in HBV-infected human liver samples. TBBz decreased the phosphorylation of hLa, which coincided with decreased HBV expression. Mutant hLa Ala(366) had reduced viral expression compared with hLa Ser(366) treatment in hLa siRNA knockdown cells. Knockdown of CK2 also decreased the HBV parameters. hLa plays a key role in the regulation of HBV gene expression in a CK2-dependent mechanism via phosphorylation of hLa at Ser(366).