BackgroundSmad4,a key intracellular mediator in transforming growth factor-β (TGF-β)signaling,plays a critical role in the normal development of many tissues/organs.However,its functional role in the development of lacrimal gland has rarely been reported.ObjectiveThe aim of this study was to investigate the role that Smad4 may play in the development of lacrimal glands using Smad4 conditional knockout (CKO) mice( C57BL/6 mouse line),MethodsSmad4 in lacrimal glands,as well as in the lens,cornea and ectoderm of the eyelids,was conditionally inactivated by the Pax6 promoter-driven Cre transgenic mice and Smad4 conditional gene mice,LacZ reporter was used to visualize the developing lacrimal gland by X-gal staining,and standard histological approaches were used to reveal morphological changes.Six or more mice or embryos in each group were used for comparisons at the same stage.ResultsLacZ staining showed that E15.0,Smad4 CKO mice could still develop primary lacrimal bud,but much shorter than the wild-type ones.At E16.5,the primary lacrimal bud in wild-type mice began branching,but no branching was found in Smad4 CKO mice except that the primary lacimal bud became blunt at the tip.At E18.0,although Smad4 CKO mice develop some acini,the branching and size and number of acini were obviously less than ones in Smad4 wild-type mice.Based on histological findings,lacrimal glands in Smad4 CKO mice developed slowly,and the size was considerably smaller,and the numbers of lobes as well as the numbers of acini were much fewer than those of Smad4 wild-type mice lacrimal glands at various stages.Pigment and adipose tissue were also observed within the lacrimal glands starting from P7 in Smad4 CKO mice and increased with age growing.Lacrimal glands in mutant adult mice were eventually replaced by adipose tissue and accumulation of pigments.Conclusions These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG and may be involved in the metabolism of pigment and adipose tissue in LG.

Objective To study the effects of the cytotoxicity, cell cycle and time dependent apoptosis of Jurkat T lymphoma cells induced by Tripterygium Hypoglaucum (Levl) Hutch (THH) alkaloids so ad to explore the mechanisms of the apoptosis induced by the THH alkaloids. Methods Cell vitality and cell proliferation were measured by Typan blue staining. Cell cycle and the time dependent apoptosis were determined by DNA staining, TUNEL labeling and flow cytometry. Results THH alkaloids could effectively inhibit cell proliferation of Jurkat cells and induce the G 1 arrest and could induce apoptosis in G 2/S phase first and then G 1 phase. Conclusion THH alkaloids can inhibit DNA synthesis, cell proliferation and can also induce apoptosis of Jurkat T lymphoma cells in all phases.

INTRODUCTIONThis prospective study aims to evaluate botulinum toxin type A (BTX-A, Botox ®) as a treatment for idiopathic detrusor overactivity (IDO) for patients with symptoms of overactive bladder (OAB).

MATERIALS AND METHODSNineteen patients with IDO were treated with intradetrusal injection of 200 units of BTX-A under cystoscopic guidance. There were 10 males and 9 females, with a mean age of 60 years (range, 38 to 87). Subjective responses were measured using the International Prostate Symptom Score and quality of life (QOL) score, as well as incontinent episodes, functional capacity and voiding intervals obtained from the voiding diary. They were recorded prior to, and at 6 weeks, 3, 6 and 9 months after BTX-A injections. Urodynamic studies were performed between 6 weeks to 3 months post-treatment.

RESULTSThere was statistically significant improvement in subjective parameters at 3 months post-treatment involving QOL (P = 0.002), incontinence episodes (P = 0.004), functional capacity (P = 0.01) and voiding interval (P <0.001). Reflex volume was significantly increased (P = 0.003), and maximal detrusal pressure (P = 0.001) as well as leak volume (P = 0.013) were significantly decreased during follow-up. Results of a gender-based subgroup analysis reveal that BTX-A may be more efficacious in females. Observed side effects included a patient who needed to perform CISC for about 3 months, a patient who had gross haematuria needed bladder washout and 3 patients who required treatments for urinary tract infection.

CONCLUSIONOverall BTX-A, which is well received by most patients, has become a very important part of the armamentarium for the treatment of IDO.

Adult ; Aged ; Aged, 80 and over ; Botulinum Toxins, Type A ; therapeutic use ; Female ; Health Status Indicators ; Humans ; Male ; Middle Aged ; Neuromuscular Agents ; therapeutic use ; Quality of Life ; psychology ; Urinary Bladder ; cytology ; Urinary Bladder, Overactive ; drug therapy ; psychology ; Urodynamics

Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic option,and the recurrence rate is extremely high(＞50％within 3 years).A newly discovered chromosomal deletion that occurs in the majority of FLCs generates a novel kinase fusion between DnaJ heat shock protein family member B1(DNAJB1)and protein kinase cAMP-activated catalytic subunit alpha(PRKACA)(DNAJB1-PRKACA).Despite its high penetrance and apparent specificity for FLC,the oncogenic role of this fusion event remains unclear.In this review article,we discuss the histology,presentation and diagnosis,current treatment,and roles of the DNAJB1-PRKACA as well as research models contributing to our understanding of this disease.

OBJECTIVETo assess the magnitude of overweight and obesity and its associated sociodemographic factors in adolescents attending junior high schools in Xi'an, Shanxi province.

METHODSA total of 1 804 adolescents attending junior high schools in Xi'an (age: 11-17 years) were enrolled randomly from 30 schools in 6 districts in Xi'an. Overweight and obesity was categorized with body mass index (BMI) cutoffs from Working Group of Obesity in China (WGOC). Underweight was defined by BMI-Z < or = -2 s. Sociodemographic information was collected from the parents of the survey participants using self-administered, structured and precoded questionnaires.

RESULTSOverall 17.4% of adolescents were overweight or obese (overweight 11.2%; obesity 6.2%), but there was a marked gender difference in the prevalence with 20.2% of boys versus 14.4% of the girls being overweight or obese. The prevalence of underweight was 2.7%. In a multivariate model, age, residence, household wealth, and parents' BMI were significantly associated with overweight and obesity (P < 0.05). After having been adjusted for age and gender, the odds ratio of an adolescent being overweight and obese was 2.7 (95% CI: 1.8-4.0) folds higher in urban areas than in rural areas, and was 1.6 (95% CI: 1.04-2.5) folds higher for adolescents from rich families than those from poor families. An adolescent with one or both parents overweight was 1.8 (95% CI: 1.3-2.5) more likely to be overweight themselves compared to those with normal weight parents.

CONCLUSIONSOverweight and obesity is a major public health problem in adolescents in Xi'an. Overweight and obesity is more prevalent in younger boys from richer families living in urban districts and those whose parents were either overweight or obese.

Adolescent ; Age Factors ; Child ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Income ; Logistic Models ; Male ; Nutritional Status ; Obesity ; epidemiology ; Overweight ; Parents ; Risk Factors ; Sex Factors

Stem cell research is one of the most rapidly expanding field of medicine which provides significant opportunities for therapeutic and regenerative applications. Different types of stem cells have been isolated investigating their accessibility, control of the differentiation pathway and additional immunomodulatory properties. Bulk of the literature focus has been on the study and potential applications of adult stem cells (ASC) because of their low immunogenicity and reduced ethical considerations. This review paper summarizes the basic available literature on different types of ASC with special focus on stem cells from dental and orofacial origin. ASC have been isolated from different sources, however, isolation of ASC from orofacial tissues has provided a novel promising alternative. These cells offer a great potential in the future of therapeutic and regenerative medicine because of their remarkable availability at low cost while allowing minimally invasive isolation procedures. Furthermore, their immunomodulatory and anti-inflammatory potential is of particular interest. However, there are conflicting reports in the literature regarding their particular biology and full clinical potentials. Sound knowledge and higher control over proliferation and differentiation mechanisms are prerequisites for clinical applications of these cells. Therefore, further standardized basic and translational studies are required to increase the reproducibility and reduce the controversies of studies, which in turn facilitate comparison of related literature and enhance further development in the field.
Adult Stem Cells* ; Adult* ; Biology ; Humans ; Regenerative Medicine* ; Stem Cell Research ; Stem Cells

Type 1 diabetes mellitus (T1D) is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors (TCRs), we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes (T2D) patients and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients (P = 7.0E
08 for CD4+ T cells, P = 1.4E
04 for CD8+ T cells) and nondiabetic controls (P = 2.7E
09 for CD4+ T cells, P = 7.6E
06 for CD8+ T cells). Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients (P = 5.2E
06 for CD4+ T cells, P = 1.9E
07 for CD8+ T cells) and nondiabetic controls (P =1.7E
07 for CD4+ T cells, P= 3.3E
03 for CD8+ T cells). Furthermore, we identified a group of highly-expanded T cell receptor clones that are shared by more than two T1D patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.

OBJECTIVETo describe the current prevalence and distribution of all types of mental disorders in Zhejiang Province and use this data to develop a provincial mental health plan.

METHODSStratified multi-stage cluster randomization was used to identify 14 counties (cities), 70 townships (urban districts), 140 villages (urban neighborhoods) and 15,000 subjects > or = 15 years of age. Psychiatric nurses used an expanded version of the General Health Questionnaire (GHQ) to identify subgroups of subjects at high, moderate and low risk of having a mental disorder, then psychiatrists determined their diagnoses by administering a structured psychiatric examination (SCID) that employs American diagnostic criteria for mental disorders (DSM-IV) to 100% of high-risk, 40% of moderate-risk and 10% of low-risk subjects.

RESULTS14 639 subjects completed the screening and 4,788 completed the psychiatric examination. The adjusted overall current rate of mental disorders was 17.3% (95% CI = 16.0%-18.7%), which dropped to 13.4% (12.2%-14.7%) if the non-specific (NOS) disorders were excluded. The most common diagnostic groups were affective disorders (8.6%, 7.9%-9.5%), anxiety disorders (4.3%, 3.6%-5.1%), and substance use disorders (3.0%, 2.4%-3.8%). The most common specific disorders were major depressive disorder (4.3%, 3.7%-4.9%), alcohol use disorder (2.9%, 2.3%-3.7%), dysthymia (1.6%, 1.3%-1.9%) and specific phobias (1.2%, 0.8%-1.8%). The overall prevalence was higher in rural than in urban areas (RR = 1.23, 95% CI = 1.11-1.37) and slightly higher in women than in men (RR = 1.11, 1.00-1.22).

CONCLUSIONSMental disorders seriously affect the social and economic development of Zhejiang Province; they are a major public health problem that urgently needs to be addressed. To do this, it is necessary to develop and implement a comprehensive province-wide mental health plan and regularly evaluate its effectiveness.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Male ; Mental Disorders ; diagnosis ; epidemiology ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Young Adult

BACKGROUNDThe purpose of this study was to assess the morphological changes and physiological function of coronary arteries in patients presenting with chest pain but having normal coronary angiograms, using intravascular ultrasound imaging (IVUS) and intracoronary Doppler (ICD) flow measurements, in order to elucidate the mechanism of syndrome X.

METHODSA total of 126 patients [67 males, 59 females, mean age (53.1 +/- 13.0) years] who experienced chest pain but had normal coronary angiograms were included in this study. ICD flow measurements of the left anterior descending coronary artery (LAD) were performed using a Cardiometrics FloMap II system. Coronary flow velocity reserve (CFVR) was defined as the ratio of the average peak velocity during hyperemia to that at baseline, induced by an intracoronary bolus injection of 18 microg adenosine. A 3.2F or 2.9 F 30 MHz mechanical rotating ultrasound catheter (CVIS, Boston Scientific) or a 3.0 F 20 MHz electronic ultrasound catheter (Endosonics) was used for IVUS.

RESULTSThe mean CFVR value of the LAD was 2.71 +/- 0.74. Reduction of CFVR (< 3.0) was found in 82 of 126 (65.1%) patients. IVUS images of the LAD were available for 109 patients. Plaque formation was detected in 76/109 (69.7%) patients. Based on the presence or absence of plaque formation as well as the reduction or non-reduction of CFVR, patients were divided into four groups: Group I (n = 10), normal IVUS findings and normal CFVR; Group II (n = 23), normal IVUS findings with reduction in CFVR; Group III (n = 29), IVUS evidence of plaque formation but normal CFVR; and Group IV (n = 47), IVUS evidence of plaque formation with reduction in CFVR.

CONCLUSIONThis study shows the important clinical value of a combination of IVUS and ICD in diagnosing patients with angiographically normal coronary arteries. Only 10% of patients studied (Group I) were found to be truly free of coronary disease, while 20% of patients (Group II) would be diagnosed as suffering from syndrome X.

Adult ; Aged ; Coronary Angiography ; Coronary Circulation ; Female ; Humans ; Laser-Doppler Flowmetry ; Male ; Microvascular Angina ; diagnosis ; physiopathology ; Middle Aged ; Ultrasonography, Interventional

Purpose: Carotid vessel wall volume (VWV) measurement on three-dimensional ultrasonography (3DUS) outperforms conventional two-dimensional ultrasonography for carotid atherosclerosis evaluation. Although time-saving semi-automated algorithms have been introduced, their clinical availability remains limited due to a lack of validation, particularly an extensive reliability analysis. This study compared inter-observer and intra-observer reliability between manual segmentation and semi-automated segmentation for carotid VWV measurements on 3DUS. Methods: Thirty-one 3DUS volume datasets were prospectively acquired from 20 healthy subjects, aged >18 years, without previous stroke, transient ischemic attack, or cardiovascular disease. Five observers segmented all volume datasets both manually and semi-automatically. The process was repeated five times. Reliability was expressed by the intraclass correlation coefficient, supplemented by the coefficient of variation. Results: Carotid VWV measurements using the common carotid artery (CCA) were more reliable than those using the internal carotid artery (ICA) or external carotid artery (ECA) for both manual and semiautomated segmentation (manual segmentation, CCA: inter-observer, 0.935; intra-observer, 0.934 to 0.966; ICA: inter-observer, 0.784; intra-observer, 0.756 to 0.878; ECA: inter-observer, 0.732; intraobserver, 0.919 to 0.962; semi-automated segmentation, CCA: inter-observer, 0.986; intra-observer, 0.954 to 0.993; ICA: inter-observer, 0.977; intra-observer, 0.958 to 0.978; ECA: inter-observer, 0.966; intra-observer, 0.884 to 0.937). Total carotid VWV measurements by manual (inter-observer, 0.922; intra-observer, 0.927 to 0.961) and semi-automated segmentation (inter-observer, 0.987; intra-observer, 0.968 to 0.989) were highly reliable. Semi-automated segmentation showed higher reliability than manual segmentation for both individual and total carotid VWV measurements. Conclusion 3DUS carotid VWV measurements of the CCA are more reliable than measurements of the ICA and ECA. Total carotid VWV measurements are highly reliable. Semi-automated segmentation has higher reliability than manual segmentation.