[Curative effects of bi-pedicled deep inferior epigastric perforator flap in repairing large soft tissue defects in the lower limbs].

Objective: To investigate the curative effects of bi-pedicled deep inferior epigastric perforator (DIEP) flap in repairing large soft tissue defects in the lower limbs. Methods: A retrospective observational study was conducted. From February 2016 to June 2020, 16 patients with large soft tissue defects in the lower limbs caused by trauma or after tumor/scar resection were admitted to the Department of Hand Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, including 9 males and 7 females, aged 25-58 years, with the area of soft tissue defects ranging from 14.0 cm×8.0 cm to 32.0 cm×18.0 cm. Using the abdomen as the donor site, the conjoined abdominal wall flap, i.e., the bi-pedicled DIEP flap (with an area ranging from 15.0 cm×9.0 cm to 32.0 cm×20.0 cm) carrying two sets of the trunk of the deep inferior epigastric artery was designed and resected to repair the wound. The donor site wound was sutured directly. The flap survival and wound healing in the donor and recipient areas were observed after operation. The curative effect was evaluated during the follow-up. At the last follow-up, the American Knee Society score and lower extremity functional scale were used to assess the functions of knee joint and lower limb, respectively. Results: The flaps of 15 patients survived after operation; the flap of one patient had partial infection at the edge after operation but healed after debridement and dressing change. The wounds in the donor and recipient areas of 16 patients all healed well. Follow-up of 16-28 months showed that the recipient area had a good shape and pliable texture, and there was no obvious swollen appearance, hyperpigmentation, or abnormal hair growth; the donor site had linear scar only, with no complications such as abdominal hernia or hyperplastic scar; the functions of knee joint and lower limb were well reconstructed, with no recurrence of tumor. At the last follow-up, among the 4 patients with knee joint injury, 3 cases were excellent and 1 case was good in the evaluation of knee joint function; among the 12 patients with lower limb injury, 9 cases were excellent and 3 cases were good in the evaluation of lower limb function. Conclusions: The donor site of bi-pedicled DIEP flap is concealed with abundant tissue and large area for resection, with which can be used to repair large soft tissue defects in the lower limbs, achieving good short-term results of appearance and function restoration.

[Efficacy of adrenocorticotropic hormone in children with frequently relapsing or steroid-dependent nephrotic syndrome].

Objective: To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in children with frequently relapsing or steroid-dependent nephrotic syndrome. Methods: The clinical data of 38 children with frequently relapsing or steroid-dependent nephrotic syndrome who were admitted to the Department of Nephrology, the Children Hospital, Zhejiang University School of Medicine from January 2015 to December 2020 were retrospectively analyzed. The general information, clinical manifestations, laboratory data of the children and follow-up (till 12 months after treatment) were collected. The patients were divided into ACTH group and Glucocorticoid (GC) group according to treatment plan. Cumulative remission, average recurrence rate, GC dosage, height and weight change and peripheral blood CD19+B lymphocyte count were compared between the two groups to evaluate the efficacy and adverse reactions of ACTH. Fisher's exact test, t test or rank sum test was used for comparison between groups. Results: Among the 38 patients, 28 were male and 10 were female, aged 84 (24, 180) months; 19 were in ACTH group and 19 were in GC group. The cumulative remission rate of 12 months in ACTH group was higher than that in GC group (9/19 vs. 2/19,χ²=6.81,P=0.009), the average recurrence rate was lower than that in GC group ((0.7±0.8) vs. (1.7±1.1) times, t=-3.27, P=0.011), and the average dosage of GC was lower than that in GC group ((0.27±0.16) vs. (0.51±0.27) mg/(kg·d), t=-3.21, P=0.014). The increase in height was higher than that in the GC group (4 (3,5) vs. 3 (2, 3) cm/year, Z=2.58, P=0.010), and the peripheral blood CD19+B lymphocyte count was lower than that in the GC group ((223±149)×106 vs. (410±213)×106/L,t=-3.35, P=0.009). In safety, 19 cases had transient decreased urine volume, 7 cases had hyperglycemia, and 3 cases had hypertension during the infusion of ACTH, which could be relieved after drug withdrawal. Conclusion: ACTH has a better effect on children with frequently relapsing or steroid-dependent nephrotic syndrome, which can improve cumulative sustained remission rate, lower relapses rate and decrease the dosage of GC, with good safety.

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

Long noncoding RNA LINC00511 involves in breast cancer recurrence and radioresistance by regulating STXBP4 expression via miR-185.

OBJECTIVE: The aim of this study was to explore the molecular function of long intergenic noncoding RNA 00511 (LINC00511) and its target proteins in recurrent breast cancer after breast-conserving surgery followed by radiotherapy. PATIENTS AND METHODS: LINC00511 expression in tissues was measured by quantitative polymerase chain reaction (qPCR). The association between LINC00511 expression and the clinicopathological features of breast cancer was analyzed by Chi-square tests. The impact of LINC00511 on overall survival was evaluated by the log-rank test. MDA-MB-231/MDA-MB-436 cell lines transfected with short hairpin RNA (shRNA) were used to investigate the influence of LINC00511 silencing on tumor growth and radiosensitivity in vitro and in vivo. A series of experiments including cell apoptosis assay, cell colony formation assay, and mouse xenograft models were applied to test those transfected cell lines. MicroRNA (miRNA) targets of LINC00511 were identified by bioinformatics analysis and further validated by dual luciferase reporter assay, qPCR, and Western blot analysis. RESULTS: LINC00511 expression was significantly increased in breast cancer tissues and correlated with recurrence and poor survival after breast-conserving surgery followed by radiotherapy. LINC00511 knockdown by shRNA restricted cell proliferation, promoted cell apoptosis, and enhanced radiosensitivity in vitro, and inhibited tumor growth with an increased response to radiation in vivo. In addition, elevated LINC00511 was found to increase syntaxin-binding protein 4 (STXBP4) expression through competitive binding to miR-185, while silencing LINC00511 decreased STXBP4 expression and increased radiosensitivity. CONCLUSIONS: LINC00511 inhibition impairs its competitive binding to miR-185, resulting in increased STXBP4 expression and improved radiation response in breast cancer. Our study results suggest that the LINC00511/miR-185/STXBP4 axis may be a promising therapeutic target for improving the prognosis of breast cancer.

Long noncoding RNA FAM201A involves in radioresistance of non-small-cell lung cancer by enhancing EGFR expression via miR-370.

OBJECTIVE: The aberrant expression of long noncoding RNAs (lncRNAs) is involved in the molecular regulation of non-small cell lung cancer (NSCLC). This study aims to investigate the biological interaction of lnc-FAM201A and its downstream factors and their impacts on the radiotherapy response of NSCLC. PATIENTS AND METHODS: Quantitative Polymerase Chain Reaction (qPCR) was used to determine the expression of FAM201A in NSCLC tissues. The Chi-square tests explored the association between FAM201A level and the poor clinicopathological characteristics (including radioresistance) of NSCLC. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various prognostic factors for overall survival (OS). The effect of FAM201A on OS was tested by the log-rank test. A549/SK-MES-1 cell lines transfected with short hairpin RNA (shRNA) were used to verify the promoting effects of FAM201A on radiotherapy resistance in vitro and in vivo. Cell apoptosis (analyzed by flow cytometry), cell proliferation (determined by Cell Counting Kit-8), and mice xenograft models were performed to confirm the results. The downstream targets of FAM201A were predicted by bioinformatics tools. Additionally, the Dual-luciferase reporter assay, qPCR, and Western blotting were performed to confirm their interaction. RESULTS: FAM201A was significantly upregulated in tissues obtained from NSCLC patients resistant to radiotherapy. Increased FAM201A expression was strongly associated with radioresistance and inferior survival in NSCLC, as demonstrated by clinical data. The silence of FAM201A could inhibit cell proliferation and further cell apoptosis of NSCLC cells under X-ray irradiation both in vitro and in vivo. Moreover, by competitively targeting miR-370, FAM201A elevated the epidermal growth factor receptor (EGFR) and the hypoxia-inducible factor 1alpha (HIF-1α) levels. After FAM201A knockdown, EGFR and HIF-1α were repressed with enhanced radiosensitivity. CONCLUSIONS: The interference of FAM201A impairs its suppression of miR-370, resulting in the upregulation of EGFR and HIF-1α and enhancement of radiosensitivity in NSCLC patients. Collectively, our results indicated that this regulatory axis might serve as a potential therapeutic target to increase the sensitivity of radiotherapy in NSCLC patients.

Occupational health management system: A study of expatriate construction professionals.

Due to its direct impact on the safety and function of organizations, occupational health has been a concern of the construction industry for many years. The inherent complexity of occupational health management presents challenges that make a systems approach essential. From a systems perspective, health is conceptualized as an emergent property of a system in which processes operating at the individual and organizational level are inextricably connected. Based on the fundamental behavior-to-performance-to-outcome (B-P-O) theory of industrial/organizational psychology, this study presents the development of an I-CB-HP-O (Input-Coping Behaviors-Health Performance-Outcomes) health management systems model spanning individual and organizational boundaries. The model is based on a survey of Hong Kong expatriate construction professionals working in Mainland China. Such professionals tend to be under considerable stress due not only to an adverse work environment with dynamic tasks, but also the need to confront the cross-cultural issues arising from expatriation. A questionnaire was designed based on 6 focus groups involving 44 participants, and followed by a pilot study. Of the 500 questionnaires distributed in the main study, 137 valid returns were received, giving a response rate of 27.4%. The data were analyzed using statistical techniques such as factor analysis, reliability testing, Pearson correlation analysis, multiple regression modeling, and structural equation modeling. Theories of coping behaviors and health performance tend to focus on the isolated causal effects of single factors and/or posits the model at single, individual level; while industrial practices on health management tend to focus on organizational policy and training. By developing the I-CB-HP-O health management system, incorporating individual, interpersonal, and organizational perspectives, this study bridges the gap between theory and practice while providing empirical support for a systems view of health management.

Primary spinal melanoma of extramedullary origin: a report of three cases and systematic review of the literature.

STUDY DESIGN: A review of the literature and three case reports. OBJECTIVES: Primary spinal melanoma (PSM) of extramedullary origin is a rare malignant condition with limited current literature in regards to its clinical course, magnetic resonance imaging (MRI) findings, treatment strategies and prognosis. We reported here three cases of PSM of extramedullary origin. SETTING: China, Guangzhou. METHODS: We report three cases of PSM of extramedullary origin. The clinical and radiological findings of these cases were retrospectively analyzed. RESULTS: The three cases were all of males aged 39, 47 and 76 years, respectively. The duration of their symptoms was 3 weeks, 2 months and 11 months respectively. The extramedullary tumors were all well-defined solitary tumors and were located at C4-5, L2-3 and T9-10, respectively. In one case, involvement of the intervertebral foramen was found. Preoperative MRI showed hyperintense T1W signals and hypointense T2W signals in all three cases and all tumors were clinically misdiagnosed as schwannomas. The patients received total or subtotal resection surgery without radiotherapy or chemotherapy. Patients were alive at 18 months, 27 months and 36 months postoperative follow-up, respectively. CONCLUSION: PSM of extramedullary origin is a rare malignant tumor that shows characteristic findings on MRI. Surgical resection is the preferred treatment strategy.

Research on the Diffusion Law of Oncomelania Along with the Flow Through a Side-weir.

Schistosomiasis is a parasitic disease mostly found in areas along the Changjiang River, Oncomelanias is the only intermediate host of schistosomiasis. Oncomelania entering into farmland or the residential zones through the flood discharge or irrigation system is the main reason of spreading schistosomiasis. Therefore it is most essential and effective way to control diffusion of oncomelanias along with flow for preventing epidemic of schistosomiasis disease. In order to simulate the flood discharge when the river dike break or the flow from main to branch channel, a side-weir flow system is set up in this paper, And furtherly the flow characteristic is studied by experiment and mathematical modeling, Finally the research on the diffusion law of oncomelania along with side-weir flow is carried out using the experimental test. The results show that oncomelanias do not equally distribute at floodplain areas, but place where flow velocity is small, i.e. in the vortex areas during oncomelanias moving along with side-weir flow. The settling positions of oncomelanias are obtained, Which lay a good foundation for eliminating oncomelanias.

AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma.

Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.

Forkhead box P3+ T cells express interleukin-17 in nasal mucosa of patients with both allergic rhinitis and polyposis.

The pathogenesis of nasal polyposis remains unclear; it severely affects patients' quality of life and complicates inflammation in adjacent organs such as sinusitis and asthma. Aberrant immune regulatory function in these patients is proposed. The present study aims to examine the regulatory T cells (T(reg) ) in nasal mucosa of patients with allergic rhinitis (AR) and nasal polyposis (NP). Patients with AR or AR/NP were treated with inferior turbinectomy for their inferior turbinate hyperplasia. Surgically removed nasal mucosa was collected to examine the T(reg) by immunohistochemistry and flow cytometry. The results showed that more forkhead box P3 (FoxP3)(+) cells were found in AR with polyps than in those with AR alone. Further studies revealed that these FoxP3(+) T cells from AR/NP group also expressed interleukin (IL)-17. In vitro study showed that staphylococcal enterotoxin B (SEB) induced CD4(+) FoxP3(+) T cells to become FoxP3(+) IL-17(+) cells via facilitating the expression of IL-6, that in synergy with transforming growth factor-beta, induce the expression of IL-17 in FoxP3(+) cells. We conclude that FoxP3(+) IL-17(+) T cells were localized in the nasal mucosa of patients with AR and NP. SEB may play a role in converting FoxP3(+) T(reg) to FoxP3(+) IL-17(+) T cells. The presence of IL-17(+) FoxP3(+) T cells may play a role in the remodelling of the nasal airways in certain people who develop polyps, irrespective of whether or not they are atopic.

Error in the description of foot kinematics due to violation of rigid body assumptions.

Kinematic data from rigid segment foot models inevitably includes errors because the bones within each segment move relative to each other. This study sought to define error in foot kinematic data due to violation of the rigid segment assumption. The research compared kinematic data from 17 different mid and forefoot rigid segment models to kinematic data of the individual bones comprising these segments. Kinematic data from a previous dynamic cadaver model study was used to derive individual bone as well as foot segment kinematics. Mean and maximum errors due to violation of the rigid body assumption varied greatly between models. The model with least error was the combination of navicular and cuboid (mean errors < = 1.3 degrees, average maximum error < = 2.4 degrees). Greatest error was seen for the model combining all the ten bones (mean errors < = 4.4 degrees, average maximum errors < = 6.9 degrees). Based on the errors reported a three segment mid and forefoot model is proposed: (1) Navicular and cuboid, (2) cuneiforms and metatarsals 1, 2 and 3, and (3) metatarsals 4 and 5. However the utility of this model will depend on the precise purpose of the in vivo foot kinematics research study being undertaken.

Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa.

BACKGROUND: The prevalence of airway inflammatory disorders keeps rising; its pathogenic mechanism is still not fully understood. OBJECTIVE: The present study aimed to investigate the role of muscarinic receptor (M receptor) in regulating the immune cell activity in nasal mucosa by using surgical removed nasal mucosa from patients with nasal polyposis (NP) as a study platform. METHODS: Human nasal mucosal sample was collected from inferior turbinectomy of 86 patients with NP or/and allergic rhinitis. Expression of tumor necrosis factor alpha (TNF-alpha), M receptor, OX40 ligand was measured in nasal mucosa by enzyme-linked immunosorbent assay, flow cytometry, and Western blotting assay. RESULTS: When compared with non-NP (nNP) nasal mucosa, contents of TNF-alpha and TNF-alpha+ cells markedly increased in NP nasal mucosa; immune staining colocalized M3 receptor+ and TNF-alpha+ cells in NP nasal mucosa; exposure of isolated CD4+ T cells to methacholine induced the release of TNF-alpha. We also found CD11c+/M3 receptor+ cells in NP nasal mucosa. Methacholine increased the expression of OX40L in dendritic cells. Staphylococcal (S) aureus and S. enterotoxin B (SEB) were detected in NP nasal mucosa. Exposure of dendritic cells or naïve CD4+ T cells to SEB initiated the expression of M3 receptor at mRNA and protein levels. CONCLUSIONS: The present data demonstrate that parasympathetic activity has the capacity to activate dendritic cells to release OX40 ligand, the latter induces CD4+ T cells to produce IL-4 and TNF-alpha that may further contribute to the pathogenesis of NP.

Lifespan influences on mid- to late-life cognitive function in a Chinese birth cohort.

OBJECTIVE: To explore factors throughout the lifespan that influence cognition in midlife to late life. METHODS: We conducted a retrospective birth cohort study of 2,062 individuals born during 1921-1954 in Beijing, China. In 2003-2005, birth records were abstracted, and participants then 50-82 years old received standardized examinations for health, cognition, and socio-environmental measures. Using cumulative logit models, we assessed adjusted relative effects of prenatal, early life, and adult factors on mid- to late-life cognition. RESULTS: Most prenatal factors were associated with mid- to late-life cognition in the unadjusted models. However, when childhood and adult factors were sequentially added to the models, the impact of prenatal factors showed successive attenuation in effect size, and became insignificant. In contrast, early life factors remained significantly associated with mid- to late-life cognition even after full life-course adjustments. Specifically, those whose fathers had laborer vs professional occupations (odds ratio [OR](Laborer) 1.74; 95% confidence interval [CI]: 1.25-2.42) had poorer cognitive outcomes, while individuals who drank milk daily in childhood (OR 0.65; 95% CI: 0.54-0.80), had more years of education (OR(10-12 years) 0.60; 95% CI: 0.45-0.81; OR(13+ yrs) 0.29; 95% CI: 0.23-0.38), and were taller adults (OR(height > or = SD) 0.65; 95% CI: 0.49-0.86) had better cognition. The high prenatal risk infants had similar patterns with a trend toward a stronger association between cognition and socioenvironmental factors. CONCLUSION: Mid- to late-life cognition is influenced by factors over the entire lifespan with the greatest impact coming from early life exposures. Nutrition, education, social, and family environment in early life may have a long-term impact on cognition in developing countries.

Kimura disease: a case report and review of the Chinese literature.

BACKGROUND: Kimura disease, often accompanied by nephrotic syndrome, is a rare, chronic inflammatory disorder of unknown cause. In this report, the clinical and histopathological characteristics of 20 Chinese patients with Kimura disease-associated nephrotic syndrome were retrospectively evaluated. METHODS: We report a case of Kimura disease that was diagnosed recently in our ward, with steroid-responsive but recurrent minimal-change nephrotic syndrome. Meanwhile, we also used three powerful Chinese journal search engines (Cqvip.com, Wanfang.data and ScienceChina) to search the cases reported in Chinese from 1984 to 2007. RESULTS: The nephrotic syndrome of our patient occurred 20 months after the onset of Kimura disease. Renal biopsy revealed minimal-change lesions. The patient was responsive to the steroid, but proteinuria recurred. In most of the 19 other cases, the onset of nephrotic syndrome occurred after subcutaneous masses. Renal biopsy in 13 cases showed mesangial proliferative glomerulonephritis in 9, minimal change disease in 2 and membrane nephropathy in 2 cases. Serum creatinine levels were elevated in 5 patients. CONCLUSION: Normally, Kimura disease-associated nephrotic syndrome patients are sensitive to prednisone therapy but are likely to relapse. In patients with recurrent nephrotic syndrome, renal insufficiency is not uncommon.

In vitro study of foot kinematics using a dynamic walking cadaver model.

There is a dearth of information on navicular, cuboid, cuneiform and metatarsal kinematics during walking and our objective was to study the kinematic contributions these bones might make to foot function. A dynamic cadaver model of walking was used to apply forces to cadaver feet and mobilise them in a manner similar to in vivo. Kinematic data were recorded from 13 cadaver feet. Given limitations to the simulation, the data describe what the cadaver feet were capable of in response to the forces applied, rather than exactly how they performed in vivo. The talonavicular joint was more mobile than the calcaneocuboid joint. The range of motion between cuneiforms and navicular was similar to that between talus and navicular. Metatarsals four and five were more mobile relative to the cuboid than metatarsals one, two and three relative to the cuneiforms. This work has confirmed the complexity of rear, mid and forefoot kinematics. The data demonstrate the potential for often-ignored foot joints to contribute significantly to the overall kinematic function of the foot. Previous emphasis on the ankle and sub talar joints as the principal articulating components of the foot has neglected more distal articulations. The results also demonstrate the extent to which the rigid segment assumptions of previous foot kinematics research have over simplified the foot.

An aqueous extract of the popular Chinese nutraceutical Kwei Ling Ko (Tortoise shell-Rhizome jelly) activates the PPARgamma pathway and down-regulates the NFkappaB activity.

It is generally believed that the popular nutraceutical 'Kwei Ling Ko' (KLK; Tortoise shell-Rhizome jelly) has antiinflammatory effects, but the mechanism by which its effects are manifested remains unknown. Peroxisome proliferation-activated receptors (PPARs) are members of the nuclear hormone receptor/transcription factor superfamily with multiple roles in adipocyte differentiation, glucose homeostasis, immunomodulation and antiinflammatory regulation. As PPAR is required for adipocyte induction, we used adipogenesis as a possible screen for the activation of the PPAR pathway. Interestingly, an aqueous extract of KLK (sKLK) was able to induce the adipocyte differentiation of fibroblast cell lines. Adipogenesis was confirmed by flow cytometric analysis using a fluorescent lipid stain. Up-regulation of PPARgamma transcripts during adipogenesis was also demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). The sKLK-induced adipogenesis was similar to that elicited by insulin. The activity of nuclear factor-kappaB (NFkappaB), a transcription factor responsible for the regulation of proinflammatory genes, was also down-regulated in response to sKLK. Luciferase reporter gene assays further demonstrated that sKLK inhibited both basal and tumor necrosis factor-alpha-stimulated NFkappaB activation. The activities reported in this study support an immunomodulatory effect for sKLK. As activation of PPAR pathway has a dual role in adipogenesis and anti-inflammation, our observations are consistent with the notion that KLK possesses antiinflammatory properties.

Thanatophoric dysplasia type I.

Thanatophoric dysplasia is a sporadic, nearly always lethal congenital skeletal dysplasia. It is characterized by shortening of the limbs, a severely small thorax, macrocephaly, and platyspondyly. There are two major subtypes: a short, curved femur characterizes type I, and a straighter femur with cloverleaf skull characterizes type II. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR-3) gene have been identified in both subtypes, which suggest that thanatophoric dysplasia is a genetically homogenous skeletal disorder. Most affected neonates die of respiratory failure, due to narrow thorax with pulmonary hypoplasia. Antenatal sonographic diagnosis is feasible in the second trimester of pregnancy, but differentiating thanatophoric dysplasia from non-lethal skeletal disorders is very important. At the present time, however, prenatal genetic screening seems unpractical.

Use of electron microscopic evaluation for the diagnosis of adrenal cortical carcinoma in fine needle aspiration cytology: a case report and review of the literature.

Bilateral adrenal tumors were detected in a 72-year-old man who had a history of hepatic inflammatory pseudotumor. Computet tomography (CT)-guided fine needle aspiration cytology (FNAC) of the adrenal glands was performed. The cytologic findings were similar to the previous diagnosis of "inflammatory pseudotumor" in the liver. However, the origin of some aggregated large atypical cells observed in the adrenal FNAC specimens was not known. Immunocytochemically, these large atypical cells were positive for vimentin and negative for cytokeratin and chromogranin A. An electron-microscopic study showed that these large atypical cells contained mitochondria with tubulovesicular cristae and smooth endoplasmic reticulum arranged in whorled and laminated patterns, and these findings confirmed diagnosis of primary adrenal cortical carcinoma. The histopathological diagnosis of the resected bilateral adrenal tumor was adrenal cortical carcinoma. The patient died 7 months after surgery, with recurrence of the bilateral adrenal cortical carcinoma and extensive metastases. A diagnosis of primary adrenal cortical carcinoma with extensive metastases was finally demonstrated by autopsy. Retrospectively, the previous liver tumor was determined to be a metastatic lesion.

Heat shock cognate-70 gene expression declines during normal aging of the primate retina.

PURPOSE: Despite documented age-related changes in retinal function and histology, little is known about the pattern of gene expression during normal aging of the vertebrate retina. This study was undertaken to definitively characterize gene expression in the primate retina during aging. METHODS: Human retina cDNA library clones were arrayed at high density on nylon membranes and screened with mixed cDNA probes generated from young (4-year-old) and old (80-year-old) human retinae. Clones showing a more than twofold difference in intensity were rescreened by dot blot analysis with the same probes and with mixed cDNA probes generated from young (2-3 years) and old (27-35 years) rhesus monkeys. One clone identified by its differential (age-putative) signal, and age-related differential expression was used for analysis of Northern blot analysis of total retinal RNA from human donors (35 weeks to 94 years of age) and two rhesus monkeys (2 and 27 years of age). The identified clone was sequenced and compared with entries in the GenBank/EMBL databases. Western blot analysis was performed on protein isolated from the retina of human donors aged 4 to 64 years and rhesus monkeys aged 18 months and 35 years. RESULTS: Approximately 1.6% of the 55,368 retina-expressed sequences examined show age-related changes between tissues from young and old donors. The mRNA level one clone, identical with heat shock cognate (HSC)70, was altered during normal retinal aging in primates. Regression analysis of Northern blot analysis signals from 23 human donors suggested that there may be a two- to threefold decrease in HSC70 mRNA levels in the human retina by the eighth decade of life. Western blot analysis also showed lower levels of the 70-kDa HSC protein in older tissues of both primates. CONCLUSIONS: HSC70 mRNA levels apparently decline during normal aging of the primate retina. Because the heat shock 70 protein family may play important roles in ocular development and protection from various biologic and environmental stresses, decreased HSC70 levels in the retina during aging may contribute to the apparent increased susceptibility of the retina to age-acquired retinal disease.