SMARCA4­deficient uterine adnexal tumor with ascites: A case report and literature review.

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4)-deficient tumors are rare and highly aggressive tumors characterized by a loss of SMARCA4 expression, and SMARCA4-deficient tumors in the adnexal area of the uterus are particularly rare. The present study describes the case of a 64-year-old woman who was admitted to Weifang People's Hospital (Weifang, China) with abdominal distension, and was observed to have a mass with ascites in the adnexal area of the uterus. Based on clinical, imaging and pathological findings, the patient was diagnosed with a SMARCA4-deficient adnexal tumor with ascites. Biopsy of the left and right adnexal lesions was performed, and the patient was administered chemotherapy. After one cycle of bevacizumab, sindilizumab and carboplatin, no further treatment was administered. After biopsy and chemotherapy, the abdominal distension was alleviated and the general condition of the patient was satisfactory. The patient was followed up and died 3 months after treatment. Notably, it is important to avoid misdiagnosing this tumor as other types of adnexal uterine tumors, and morphological and immunohistochemical features may be useful for diagnosing primary SMARCA4-deficient tumors in the adnexal area of the uterus.

[Expression Changes of Hypoxia-Inducible Factor-1α in G-CSF Induced Hematopoietic Stem Cell Mobilization].

OBJECTIVE: To investigate the expression and its relative mechanism of hypoxia-inducible factor-1α(HIF-1α) in bone marrow(BM) of mice during G-CSF mobilization of hematopoietic stem cells (HSC) . METHODS: Flow cytometry was used to detect the proportion of Lin-Sca-1+ c-kit+ (LSK) cells in peripheral blood of C57BL/6J mice before and after G-CSF mobilization. And the expression of HIF-1α and osteocalcin (OCN) mRNA and protein were detected by RQ-PCR and immunohistochemistry. The number of osteoblasts in bone marrow specimens of mice was counted under the microscope. RESULTS: The proportion of LSK cells in peripheral blood began to increase at day 4 of G-CSF mobilization, and reached the peak at day 5, which was significantly higher than that of control group (P<0.05). There was no distinct difference in the expression of HIF-1α mRNA between bone marrow nucleated cells and osteoblasts of steady-state mice (P=0.073), while OCN mRNA was mainly expressed in osteoblasts, which was higher than that in bone marrow nucleated cells (P=0.034). After mobilization, the expression level of HIF-1α increased, but OCN decreased, and the number of endosteum osteoblasts decreased. The change of HIF-1α expression was later than that of OCN and was consistent with the proportion of LSK cells in peripheral blood. CONCLUSION: The expression of HIF-1α in bone marrow was increased during the mobilization of HSC mediated by G-CSF, and one of the mechanisms may be related to the peripheral migration of HSC induced by osteoblasts inhibition.

Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report.

BACKGROUND: Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi'an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6-31.0) and 36.1 (26.4-not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi'an site); he had received five prior lines of treatment and had extensive extramedullary lesions. CASE PRESENTATION: The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10-4) complete response status for 52 months. CONCLUSIONS: This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.

The Arabidopsis J-Protein AtDjC5 Facilitates Thermotolerance Likely by Aiding in the ER Stress Response.

AtDjC5 belongs to the J-protein family in Arabidopsis thaliana. Its biological functions remain unclear. In this study, we examined the roles of AtDjC5 in resisting heat stress using reverse genetic analysis. After the seedlings were exposed directly to 44 °C for 90 min, AtDjC5 knockout seedlings displayed decreases in the survival rate, membrane system stability, and cell vitality compared to WT seedlings, indicating that AtDjC5 is involved in plant basal thermotolerance. The AtDjC5 knockout seedlings pre-exposed to 37 °C for 30 min exhibited decreases in the survival rate and total chlorophyll contents and increased cell death when they were subsequently exposed to 45 °C compared to the WT seedlings, indicating that AtDjC5 plays an important role in plant acquired thermotolerance. AtDjC5 was found to localize to the endoplasmic reticulum. The expression of the AtDjC5 gene was induced by heat and TM (an ER stress inducer) treatment. Furthermore, we found that the knockout of AtDjC5 inhibited ER stress-induced autophagy and the expression of ER stress-related genes. Taken together, these results suggest that AtDjC5 facilitates thermotolerance, likely by aiding in the ER stress response.

Characteristics of Retained Foreign Bodies in the Tongue: A Retrospective Study of 35 Cases.

PURPOSE: There are only a few case reports of foreign bodies (FBs) in the tongue. Delayed diagnosis or misdiagnosis is commonly reported. The purpose of this study was to identify the demographic, clinical, and radiological features that might facilitate the diagnosis of retained FBs in the tongue. METHODS: A retrospective case series was performed. Clinical and imaging data of patients with FBs in the tongue at Wuhan University Hospital of Stomatology were reviewed. The outcome variable was a preliminary, radiological, intraoperative, or pathological diagnosis. Covariates included age, sex, FB-related history, symptoms and signs, duration, and computed tomography (CT) imaging features. Descriptive statistics were computed for each study variable. RESULTS: Thirty-five patients were included. The sample's mean age was 54.5 ± 11.2 years, included 19 males (54.3%). Eighty percent of the patients reported FB-related history with a mean duration of 4 weeks. More than 70% of the patients presented with tongue swelling. Approximately half of the 35 cases were preliminarily misdiagnosed, and 15 of them were initially suspected to be tumors. After CT examinations, 33 of the 35 cases were diagnosed as FB. Characteristic CT imaging feature of the FB was a radiopaque line. Most FBs were located at the anterior two-thirds and marginal area of the tongue and in an oblique direction. The depth of FB was 0.61 ± 0.42 cm. The superficial ends of most FBs were close to the surface of the dorsum and the tongue margin. CONCLUSIONS: The possibility of a retained FB should be included in the differential diagnosis of a nonhealing wound or tongue enlargement when a radiopaque line is present on CT images of patients presenting with or without FB-related history. It may be easier to detect a FB in the tongue when a CT imaging postprocessing protocol, including thin-slice reconstruction and multiplanar reformation visualization and careful interpretation, is used.

A Qualitative Exploration of the Psychological Experience of Patients Hospitalized With COVID-19.

This qualitative study describes the psychological experience of patients hospitalized with COVID-19. These patients went through 3 psychological stages: extremely uncertainties during the initial diagnostic stage, complicated feelings of negativity during the treatment stage, and positive growth in the recovery stage. It is important for nurses to provide holistic care.

Reduced Plasma Estradiol Levels are Associated with Sleep Apnea in Depressed Peri- and Post-Menopausal Women.

OBJECTIVE: This study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods. METHODS: A total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea-hypopnea index (AHI)≥5) (OSA vs non-OSA). The correlation between estradiol levels and apnea-hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone. RESULTS: Among the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p<0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875-0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826-0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012-1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389-4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136-2.353, p = 0.008) are correlated with OSA. CONCLUSION: The ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.

Decreased ALCAM expression and promoter hypermethylation is associated with preeclampsia.

Preeclampsia (PE) is a major obstetrical complication that results in maternal and fetal morbidity and mortality. Aberrant epigenetic modifications are widely involved in the pathogenesis of PE. Previously, the activated leukocyte cell adhesion molecule (ALCAM) was reported to be required for blastocyst implantation but has not been described in the context of pathological pregnancy. This study explored the expression of ALCAM and its methylation levels in the placentas and peripheral venous blood of patients with PE from a Chinese Han population. The mRNA and protein expression levels of ALCAM were downregulated in the PE placentas compared with the control placentas (P < 0.05). The methylation rate of the ALCAM gene promoter was considerably elevated in the placentas (P = 0.003, odds ratio (OR) = 0.264, 95% confidence interval (95% CI) [0.108-0.647], cases n = 47, controls n = 53) and peripheral blood (P = 0.007, OR = 0.455, 95% CI [0.256-0.806], cases n = 100, controls n = 100) of the PE patients compared with those of the normotensive women, suggesting a negative relationship between ALCAM methylation and gene transcription. Moreover, the transcriptional expression of ALCAM was dramatically increased by demethylating treatment in trophoblastic cells. ALCAM is expected to be involved in the pathogenesis of PE through methylation regulation.

The collaboration and reporting quality of social welfare systematic reviews in the Campbell Collaboration online library.

BACKGROUND: To analyze the collaboration and reporting quality of the systematic reviews of social welfare in the Campbell collaboration online library. METHODS: The Campbell collaboration online library was searched for systematic reviews of social welfare and the basic information extracted in order to assess the reporting quality of systematic reviews using a MOOSE checklist. BICOMS-2 and UCINET software were used to produce the social network, and Comprehensive Meta Analysis (Version 2) and STATA 13.0 were used to analyze the related data. RESULTS: Fifty-seven systematic reviews of social welfare were included. Twenty-eight items of the included social welfare systematic reviews were rated as complete (≥70%). There were significant differences between ≤2013 and ≥ 2014 in five items. These differences were as follows: research published by one organization or more than one organization in one item, more than three authors or less than four authors in two items, and one country or more than one country in six items. It's completed about researches with more than one organization, three authors or more than one country. Some items were found to have a low reporting rate of studies published before 2014, by one organization, with less than four authors or one country, respectively. The social network of authors and organizations showed good collaboration. CONCLUSIONS: Some items could be further improved with regard to the rate of reporting systematic reviews of social welfare in the Campbell collaboration online library. This could improve the overall quality of social welfare systematic reviews.

Identification of high expression profiles of miR-31-5p and its vital role in lung squamous cell carcinoma: a survey based on qRT-PCR and bioinformatics analysis.

BACKGROUND: The function of miR-31-5p in lung squamous cell carcinoma (LUSC) remains unclear, therefore, a systematic study was performed for the clinical significance and molecular mechanism of miR-31-5p in LUSC. METHODS: Quantitative real-time reverse transcription PCR (qRT-PCR) was utilized to test the expression level of miR-31-5p in 88 LUSC tissue samples and their matching normal tissues. Data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were also utilized to confirm the expression level and clinical value of miR-31-5p in LUSC. The potential target genes of miR-31-5p were predicted by several online predicted software. Gene ontology (GO), protein-protein interaction (PPI) and pathway analysis were utilized to investigate the underlying molecular mechanism of miR-31-5p in LUSC. RESULTS: The result from qRT-PCR found that there was significant difference of miR-31-5p between LUSC and normal tissues (P<0.001). Meanwhile, Data from TCGA also showed a higher expression of miR-31-5p in LUSC tissues than that in the normal tissues (P<0.001). on the basis of the data of GEO database, five GEO datasets indicated that the expression of miR-31-5p in LUSC tissues was significantly higher than that in normal lung tissues, include GSE51858 (P=0.025), GSE74190 (P<0.000), GSE16025 (P=0.031), GSE25508 (P=0.0.01), and GSE47525 (P=0.049). Moreover, in consideration of the meta-analysis, 1,012 clinical specimens were systematically analyzed via meta-analysis, clinical specimens were systematically analyzed via meta-analysis, and the results showed that the expression of miR-31-5p in LUSC was significantly higher than in the adjacent lung tissues (SMD =0, CI: 1.08-1.45, Z=13.30, P=0.000). In addition, result from GO and pathway analyses showed that potential target genes of miR-31-5p were significantly associated with 20 GO terms and 5 pathways, such as signal transduction, transmembrane receptor protein tyrosine kinase activity, plasma membrane and Rap1 signaling pathway. Meanwhile, we also found thatmiR-31-5p target genes were related to the Rap1 signaling pathway, Oxytocin signaling pathway and Proteoglycans in cancer. Furthermore, six hub genes were identified from PPI and three hub genes, including ADCY6, ADCY9 and EGFR, proved to coexist in the Rap1 signaling pathway, oxytocin signaling pathway and Melanogenesis simultaneously. CONCLUSIONS: According to what has been discussed above, we speculated that miR-31-5p may play a vital role in the occurrence and development of LUSC.

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

Effects of time delay and body temperature on measurements of central venous oxygen saturation, venous-arterial blood carbon dioxide partial pressures difference, venous-arterial blood carbon dioxide partial pressures difference/arterial-venous oxygen difference ratio and lactate.

BACKGROUND: Central venous oxygen saturation (ScvO2), venous-arterial blood carbon dioxide partial pressures difference (Pv-aCO2), venous-arterial blood carbon dioxide partial pressures difference/arterial-venous oxygen difference ratio (Pv-aCO2/Ca-vO2) and lactate are important parameters employed during shock resuscitation. We designed this study to confirm the effects of time delay and body temperature on measurements of these four parameters. METHODS: Arterial and central venous blood samples were simultaneously drawn by plastic syringes via indwelling intra-arterial and central venous catheters from critically ill patients. Blood gas analyses were performed on both samples and repeated after 10, 20, 30, 40, 50 and 60 min. Patients were divided into a control group and a high temperature group according to whether the body temperature was greater than 38 °C. RESULTS: A total of 30 critically ill patients were enrolled. There was a trend of increasing values for ScvO2, Pv-aCO2, Pv-aCO2/Ca-vO2 and lactate over time (P < 0.001). The ScvO2 differences were all lower in high temperature group after 10, 20, 30, 40, 50 and 60 min when compared to the corresponding differences in the control group (P < 0.05). The differences in lactate values were slightly higher in the high temperature group, relative to the control group after 20, 30, 40, 50 and 60 min (P < 0.05). CONCLUSIONS: Measurements of ScvO2, Pv-aCO2, lactate and Pv-aCO2/Ca-vO2 were affected by time delay or body temperature. We recommend that arterial and central venous blood gas samples be analyzed quickly within 10 min, especially for patients with body temperature <38 °C. TRIAL REGISTRATION: ChiCTR, ChiCTR1800014484 . Registered 16 January 2018.

Role of miR-452-5p in the tumorigenesis of prostate cancer: A study based on the Cancer Genome Atl(TCGA), Gene Expression Omnibus (GEO), and bioinformatics analysis.

BACKGROUND: MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. MATERIALS AND METHODS: We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), PANTHER pathway analyses, and a disease ontology (DG) analysis were performed to find the molecular functions of the target genes from GSE datasets and miRWalk. Finally, we validated hub genes from the protein-protein interaction (PPI) networks of the target genes in the Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA). Narrowing down the optimal target genes was conducted by seeking the common parts of up-regulated genes from GEPIA, down-regulated genes from GSE datasets, and predicted genes in miRWalk. RESULTS: Based on mining of GEO and ArrayExpress microarray chips and miRNA-Seq data in the TCGA database, which includes 1007 prostate cancer samples and 387 non-cancer samples, miR-452-5p is shown to be down-regulated in prostate cancer. GO, KEGG, and PANTHER pathway analyses suggested that the target genes might participate in important biological processes, such as transforming growth factor beta signaling and the positive regulation of brown fat cell differentiation and mesenchymal cell differentiation, as well as the Ras signaling pathway and pathways regulating the pluripotency of stem cells and arrhythmogenic right ventricular cardiomyopathy (ARVC). Nine genes-GABBR, PNISR, NTSR1, DOCK1, EREG, SFRP1, PTGS2, LEF1, and BMP2-were defined as hub genes in the PPI network. Three genes-FAM174B, SLC30A4, and SLIT1-were jointly shared by GEPIA, the GSE datasets, and miRWalk. CONCLUSIONS: Down-regulated miR-452-5p might play an essential role in the tumorigenesis of prostate cancer.

Patchouli alcohol protects against ischemia/reperfusion-induced brain injury via inhibiting neuroinflammation in normal and obese mice.

Almost all of the candidate drugs for ischemic stroke failed to be translated from bench to beside. One important reason is that animals used in experimental studies cannot mimic ischemic patients due to lack of comorbidities like hypertension, diabetes and obesity. Therefore, it is better to test candidate drugs not only in normal animals but also in animals with comorbidities. Patchouli alcohol (PA), a natural tricyclic sesquiterpene in the traditional Chinese herb Pogostemonisherba, is well recognized for its anti-inflammation function in various inflammatory diseases. And as inflammation plays a very important role in cerebral ischemia/reperfusion (I/R) injury process and determines the ultimate brain damage, we hypothesized that PA could protect against cerebral I/R injury through its anti-inflammation ability. In this study, the effects of PA on cerebral I/R injury were evaluated in normal mice and obese mice. In normal mice with cerebral I/R injury, PA treatment reduced the infarct volume and neurological deficits in a dose- and time-dependent manner. PA treatment alleviated BBB dysfunction, inhibited mRNA and protein levels of TNF-α and IL-1ß and modulated the activation of MAPKs signaling pathways. Moreover, PA also reduced infarct volume, alleviated the BBB dysfunction and inhibited inflammation in ob/ob mice with cerebral I/R injury. In conclusion, we demonstrated for the first time that PA could protect against cerebral I/R injury not only in normal mice but also in obese mice via inhibiting inflammation, suggesting that PA can be a potential drug for clinical treatment of ischemic stroke.

[Bioaccumulation and Biomagnification of Heavy Metals in Three Gorges Reservoir and Effect of Biological Factors].

Three Gorges Reservoir (TGR) reached the maximum water level (175 m) of impoundment in Oct. 2010. In order to reveal the potential influence of the greatest water-level impoundment on the heavy metal pollution in the typical waters of TGR, the content level of trace metals ( Hg, Cd and Pb) in biota and potential biomagnification along the aquatic food chain were investigated in the main stem of TGR from July 2011 to August 2012, as well as the relationship between the trace metal concentrations of aquatic consumers (fish and aquatic invertebrate) and biological factors. Our study showed that no individual data of the three trace metals in biota exceeded the edible safety criteria of aquatic products in China and FAO. In contrast with those before the impoundment of TGR, Hg showed a little higher, while Cd and Pb exhibited a little lower level after the impoundment. Trace metals in TGR exhibited relatively lower concentrations compared with those in reservoirs in other countries. Significant correlations were found between the Cd concentration and body size (body length and body weight) of Cyprinus carpio, as well as the Hg concentration and body size (body length and body weight) of Erythroculter ilishaeformis. As for feeding habits, there was statistically significant difference between trace metal concentrations in herbivorous, planktonic, omnivorous and carnivorous fish. However, no significant difference was found between the metal concentrations in fish with different habitats (pelagic, mesopelagic and benthic). Even so, the overall trend was that fish living in benthic layer had higher heavy metal concentrations than those in pelagic and mesopelagic zones. The regression slopes of log-Hg concentration versus delta(15)N, served as an indicator of trophic magnification factor (TMF). Significant correlations (P < 0.05) were observed for Hg in the food web of TGR. TMF of Hg in TGR indicated lower level (0.046-0.066) in contrast with those in the reservoirs of United States and Canada, and this was explained by the relatively lower organic carbon in the soil and sediment of TGR.

Submucosal tunnelling endoscopic resection (STER) for the treatment of a case of huge esophageal tumor arising in the muscularis propria: a case report and review of literature.

BACKGROUND AND AIMS: Endoscopic Interventional Treatment is of little trauma and less complications in the treatment of esophageal tumor and leads to faster recovery and fewer days of hospitalization. This study was aimed to investigate the safety and efficacy of endoscopic interventional therapy for huge esophageal tumor arising in the muscularis propria. METHODS: The patient was treated by submucosal tunneling endoscopic resection (STER). RESULTS: The huge esophageal tumor was resected completely by STER technique, with little trauma and less complications. The size of the resected tumor was 5.5×3.5×3.0 cm. CONCLUSION: Submucosal tunneling endoscopic resection is a safe and efficient technique for treating Huge Esophageal Tumor originating from muscularis propria layer.

Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA. CONCLUSION: UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.

Caspase-8 Mediates Amyloid-ß-induced Apoptosis in Differentiated PC12 Cells.

The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-ß 1-40 (Aß1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aß-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aß1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aß1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aß1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aß1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.

Human cytomegalovirus infection is associated with essential hypertension in Kazakh and Han Chinese populations.

BACKGROUND: We aimed to study the association between cytomegalovirus (CMV) infection and hypertension in Kazakh and Han populations from Xinjiang Province, China. MATERIAL/METHODS: We analyzed data on 800 Kazakhs (467 hypertension patients and 333 healthy control participants) and 800 Hans (482 hypertension patients and 318 healthy control participants) aged 18-84 years old. ELISA and real-time quantitative PCR coupled with restriction fragment length polymorphism analysis were applied for determining CMV infection and glycoprotein B (gB) genotypes, respectively. RESULTS: Serologic evidence of CMV infection was obtained for 95.4% and 90.1% of the Kazakhs and Hans, respectively. The CMV seroprevalence rates among the Kazakh and Han participants with hypertension were 96.8% and 89.8%, respectively. Multiple logistic regression analyses revealed statistically significant independent associations between CMV seropositivity and hypertension in Kazakh males and between CMV antibody titers and hypertension in Hans; significant relationships also existed between CMV antibody titers and blood pressure in Hans. In Kazakhs, 3 CMV gB genotypes were identified: gB2 and genotype mixtures gB1+gB2 and gB2+gB3. In Hans, 4 CMV gB genotypes were identified: gB1, gB2, gB1+gB2, and gB2+gB3. Of the 4 studied genotypes, gB2+gB3 showed a significant independent association with hypertension in Kazakh females. CONCLUSIONS: CMV infection is associated with essential hypertension in Kazakh males and Hans in Xinjiang. CMV seropositivity is associated with hypertension in Kazakh males, and CMV antibody titers are associated with blood pressure and hypertension in Han males and females. Moreover, the CMV gB2+gB3 genotype mixture is associated independently with essential hypertension in Kazakh females.

[The effect of 18beta-glycyrrhetinic acid on gap junction among cerebral arteriolar smooth muscle cells in Wistar rat and spontaneously hypertensive rat].

OBJECTIVE: This study compared Wistar rat with spontaneously hypertensive rat (SHR) on the electrophysiology and coupling force of the smooth muscle cells in the cerebral arteriolar segments and observe the influence of 18beta-glycyrrhetinic acid(18beta-GA) on the gap junctions between the arterial smooth muscle cells. METHODS: The outer layer's connective tissue of the cerebral arteriolar segments was removed. Whole-cell patch clamp recordings were used to observe the 18beta-GA's impaction on the arteriolar segment membrane's input capacitance (C(input)), input conductance (G(input)) and input resistance (R(input)) of the smooth muscle cells. RESULTS: (1) The C(input) and G(input) of the SHR arteriolar segment smooth muscle cells was much higher than the Wistar rats, there was significant difference (P < 0.05). (2) 18beta-GA concentration-dependently reduced C(input) and G(input) (or increase R(input)) on smooth muscle cells in arteriolar segment. IC50 of 18beta-GA suppression's G(input) of the Wistar rat and SHR were 1.7 and 2.0 micromol/L respectively, there was not significant difference (P > 0.05). After application of 18beta-GA concentration > or = 100 micrmol/L, the C(input), G(input) and R(input) of the single smooth muscle cells was very close. CONCLUSION: Gap junctional coupling is enhanced in the SHR cerebral arterial smooth muscle cells. 18beta-GA concentration-dependent inhibits Wistar rat's and SHR cerebral arteriolar gap junctions between arterial smooth muscle cells. The inhibitory potency is similar between the two different rats. When 18beta-GA concentration is > or = 100 micromol/L, it can completely block gap junctions between arteriolar smooth muscle cells.