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Omphalocele and gastroschisis are the two most common congenital abdominal wall defects; however, no previous study has focused on gastrointestinal and hepatobiliary tract malformations in these two conditions. This study aimed to investigate the demographic characteristics, coexisting congenital gastrointestinal and hepatobiliary tract anomalies, hospital course, and outcomes of patients with gastroschisis and omphalocele.This is retrospective chart review of all patients admitted to one tertiary medical center in Taiwan between January 1, 2000 and June 30, 2020 with a diagnosis of gastroschisis or omphalocele. The medical records were reviewed to obtain demographic data regarding coexisting gastrointestinal and hepatobiliary tract anomalies and outcomes.Of the 51 patients included, 21 had gastroschisis and 30 had omphalocele. Gastroschisis was associated with a significantly younger maternal age and a higher incidence of small for gestational age. Of the 30 patients with omphalocele, twelve had associated gastrointestinal and hepatobiliary anomalies. Seven of the 21 patients with gastroschisis had gastrointestinal anomalies, and none had hepatobiliary anomalies. Among the omphalocele patients, three (10%) had documented malrotation, and one developed midgut volvulus. Among gastroschisis patients, four patients (19%) had malrotation, and two developed midgut volvulus. There were no statistically significant differences in postoperative complications or mortality rates between those with and without gastrointestinal/hepatobiliary tract anomalies.The diversity of coexisting gastrointestinal and hepatobiliary tract anomalies is higher in the omphalocele than in gastroschisis. In addition, we demonstrate that patients with gastroschisis or omphalocele have a higher rate of intestinal malrotation and midgut volvulus.

Lung cancer is the most common cancer and the leading cause of cancer-related death worldwide. The optimal management of computed tomography (CT)-indeterminate pulmonary nodules is important. To optimize individualized follow-up strategies, we developed a radiomics nomogram for predicting 2-year growth in case of indeterminate small pulmonary nodules. A total of 215 histopathology-confirmed small pulmonary nodules (21 benign and 194 malignant) in 205 patients with ultra-high-resolution CT (U-HRCT) were divided into growth and nongrowth nodules and were randomly allocated to the primary (n = 151) or validation (n = 64) group. The least absolute shrinkage and selection operator (LASSO) method was used for radiomics feature selection and radiomics signature determination. Multivariable logistic regression analysis was used to develop a radiomics nomogram that integrated the radiomics signature with significant clinical parameters (sex and nodule type). The area under the curve (AUC) was applied to assess the predictive performance of the radiomics nomogram. The net benefit of the radiomics nomogram was assessed using a clinical decision curve. The radiomics signature and nomogram yielded AUCs of 0.892 (95% confidence interval [CI]: 0.843–0.940) and 0.911 (95% CI: 0.867–0.955), respectively, in the primary group and 0.826 (95% CI: 0.727–0.926) and 0.843 (95% CI: 0.749–0.937), respectively, in the validation group. The clinical usefulness of the nomogram was demonstrated by decision curve analysis. A radiomics nomogram was developed by integrating the radiomics signature with clinical parameters and was easily used for the individualized prediction of two-year growth in case of CT-indeterminate small pulmonary nodules. • A radiomics nomogram was developed for predicting the two-year growth of CT-indeterminate small pulmonary nodules. • The nomogram integrated a CT-based radiomics signature with clinical parameters and was valuable in developing an individualized follow-up strategy for patients with indeterminate small pulmonary nodules.

To explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS).The serum IL-6 and hs-CRP levels of the patients in both the experimental group and the standard group were measured before thrombolysis and at 1 and 24 h afterwards. National Institute of Health Stroke Scale (NIHHS) scores were also recorded at the same time points as well as at 10 and 90 d after thrombolysis, and modified Rankin Scale (mRS) scores were calculated before thrombolysis and at 10 and 90 d afterwards. The differences in all these observations before and after thrombolysis were then investigated.(1) The levels of serum IL-6 and hs-CRP in the experimental group and the standard group were higher than those in the healthy control group before thrombolysis (P 0.05), indicating that higher levels of hs-CRP and IL-6 are risk factors for WUS (P 0.05). (2) There were no significant differences in the serum hs-CRP and IL-6 levels of the patients in the experimental and standard groups before thrombolysis (P 0.05). (3) The serum IL-6 and hs-CRP levels were positively correlated with the NIHHS scores in both the experimental group and the standard group (P 0.05), and they correlated with the mRS scores at 90 d.Interleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke, and the combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.

Background Gallstones are uncommon in infants and children and Asian children are thought to have very low risk. Diagnoses have increased in recent years with the widespread use of ultrasonography (USG). This study aimed to review our experience with risk factors, complications, and treatment of pediatric gallstones in low-incidence populations. Methods We retrospectively reviewed patients younger than 18 years old diagnosed with gallstones using USG between November 2006 and December 2012 in a tertiary referral hospital in Taiwan. Demographic information including age and sex, follow-up period, USG findings, predisposing factors, complications, treatment approaches and outcomes were recorded. Results Ninety-eight children with gallstones diagnosed with USG were enrolled and reviewed in our study. Females comprised 55% of patients, with no specific gender tendency. No risk factor could be identified in 30.8% of patients. The most common risk factors were cephalosporin (CS) use, presence of a choledochal cyst (CC), and spherocytosis. CS use was not associated with a higher dissolution rate. The presence of type IVa CC implied a high rate of gallstone recurrence after Roux-en-Y hepaticojejunostomy. Complications were seen in 22.4% of patients, but only two needed emergency stone removal. Expectant management was performed in 61% of patients and 62.5% of them achieved spontaneous resolution; the stone dissolution rate was not lower than in the group treated with ursodeoxycholic acid (UDCA). Stone size was significantly decreased after UDCA use if resolution did not occur. Conclusions Pediatric gallstones showed high resolution rate, and the clinical course was largely benign. CS use was the most common risk factor and did not predict a higher dissolution rate. Type IVa CC was also an important risk factor associated with a high recurrence rate. Conservative treatment and oral UDCA may be reasonable strategies in most patients, unless complications are present.

PurposeThe purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene.Materials and MethodsQuantitative reverse transcription–polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL.Resultsp53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3′- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines.ConclusionThis study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

Rationale: Multiseptate gallbladder (MSG) is a rare congenital gallbladder anomaly. Between 1963 and June 2021, only 56 cases were reported. There is currently no treatment guideline for pediatric or adult cases of MSG. Patient concerns: A 14-year-old woman visited our out-patient clinic in September 2020 for epigastric pain that last for 6 months. Honeycomb appearance of the gallbladder was noted under ultrasonography. Diagnosis: The patient was diagnosed with MSG. The diagnosis was confirmed through computed tomography and magnetic resonance cholangiopancreatography. Interventions: Cholecystectomy was performed. Outcomes: Epigastric pain showed limited improvement after the surgery. Since she was diagnosed with gastritis at the same time, a proton-pump inhibitor was prescribed. Epigastric pain was eventually resolved. Lessons: MSG cases can undergo cholecystectomy and show good recovery without complications. However, concomitant treatment may be required to resolve in the presence of other symptoms such as epigastric pain.

Taxol is commonly used chemotherapy regimen for esophageal squamous cell carcinoma (ESCC). Study of the underlying mechanisms of Taxol chemoresistance provides better understanding of esophageal cancer treatment and may provide a rational molecular target for diagnosis and intervention. Here we showed FBXO31, which was reported to be highly expressed in ESCC and significantly associated with poor prognosis, could regulate ESCC chemosensitivity to Taxol. Silencing of FBXO31 in ESCC cells sensitized cells to Taxol treatment, evidenced by FACS analysis and TUNEL assay, showing as an increased apoptotic population in FBXO31-knockdown cells compared to the control cells. The mass spectrometry data and coimmunoprecipitation results showed FBXO31 could bind with cofilin-1. Cofilin-1 knockdown in FBXO31-overexpression cells reversed FBXO31-induced suppression of cell apoptosis, suggesting FBXO31-mediated Taxol chemoresistance is associated with cofilin-1. Furthermore, in vivo experiments confirmed that knockdown of FBXO31 sensitized ESCC to Taxol treatment. This finding substantiated a pivotal role of FBOX31 in ESCC chemoresistance, indicating that FBXO31 may be a potential indicator or target for drug resistance in ESCC.

Circular RNAs (circRNAs) have recently been reported to play crucial roles in various regulatory processes and involved in cancer onset and progression. However, the potential mechanism of circRNAs in chronic lymphocytic leukemia (CLL) remains largely unknown. Here, we observed hsa_circ_0132266 (circ_0132266), a circRNA significantly decreased in the peripheral blood mononuclear cells (PBMCs) of CLL patients compared with healthy donors, could act as an endogenous sponge of hsa-miR-337-3p (miR-337-3p) and regulate its activity, which resulted in a downstream change of target-gene PML and a consequent influence on cell viability. Taken together, our data indicated the regulatory mechanism of circ_0132266 in CLL progression through circ_0132266/miR-337-3p/PML axis, suggesting that it may serve as a biomarker as well as an exploitable therapeutic target for CLL.

Endometriosis is a common gynecological disorder characterized by chronic pelvic pain and infertility, which negatively affects women's health worldwide. AFAP1-AS1 has been implicated in endometriosis lesions recently, but its mechanism of endometriosis progression remains unclear.Endometrial stromal cells (ESCs) were used to identify the role of AFAP1-AS1 in endometriosis. The migratory capability was determined by transwell. Gene and protein expressions were identified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability and apoptosis were detected by MTT assays and flow cytometry, respectively. Luciferase report assays were used to identify the interaction of AFAP1-AS1, miR-424-5p and signal transducer and activator of transcription 3 (STAT3).AFAP1-AS1 knockdown or miR-424-5p overexpression inhibited proliferation and migration, and promoted apoptosis in ESCs. In addition, knockdown of AFAP1-AS1 repressed the expression of ki-67 and Bcl-2, and promoted the levels of cleaved caspase-3 and Bax. Furthermore, knockdown of AFAP1-AS1 inhibited the conversion of E-cadherin to N-cadherin and the expression of Snail. Moreover, AFAP1-AS1 activated the STAT3/transforming growth factor-β1 (TGF-β1)/Smad2 axis via directly targeting miR-424-5p. The regulatory effect of AFAP1-AS1 silencing in ESC migration, proliferation, and apoptosis was reversed by miR-424-5p inhibition or STAT3 overexpression.AFAP1-AS1 silencing could inhibit cell proliferation and promote apoptosis by regulating STAT3/TGF-β/Smad signaling pathway via targeting miR-424-5p in ESCs. AFAP1-AS1 may be a potential therapeutic target of controlling the progression of endometriosis.

Prognoses of persons with chronic lymphocytic leukemia (CLL) including time-to-therapy (TTT) and survival is heterogeneous. Risk factors and predictive scoring systems are mostly developed in persons of predominately European descent with CLL. Whether these systems accurately predict TTT and survival of Han Chinese with CLL is unknown. We interrogated clinical and laboratory data from 334 newly diagnosed, untreated Chinese CLL without treatment indication upon diagnosis to identify variables associated with TTT and develop a prognostic score. Binet stage, blood lymphocyte level, TP53 abnormality, unmutated IGHV, prior HBV, and EBV infections were independently associated with TTT in multivariate analyses. We constructed a prognostic score dividing subjects into cohorts with low, intermediate, and high risk from diagnosis to TTT. Median TTTs were 139 months (range, 85-189 months), 25 months (12-38 months), and 4 months (1-7 months; P-value for trend

Previous studies showed that, in chronic lymphocytic leukemia (CLL) patients with isolated 13q deletion (13q-), those carrying higher percentage of leukemic cells with 13q- had more aggressive diseases. However, the prognostic value of the percentage of leukemic cells with 13q- in Chinese CLL patients with isolated 13q- remained to be determined. Using interphase fluorescence in situ hybridization (FISH), we identified 82 patients (25.4%) with isolated 13q deletion from a cohort of 323 untreated CLL patients. Among patients with isolated 13q deletion, cases of 13q- cells ≥ 80% (13q-H) had significantly shorter time to first treatment (TTT) than those of

The emergence of antibiotic drug (like carbapenem) resistance is being a global crisis. Among those resistance factors of the β-lactam antibiotics, the metallo-β-lactamases (MBLs) is one of the most important reasons. In this paper, a series of cyclic dithiocarbamate compounds were synthesized and their inhibition activities against MBLs were initially tested combined with meropenem (MEM) by in vitro antibacterial efficacy tests. Sodium 1,4,7-triazonane-1,4,7-tris(carboxylodithioate) (compound 5) was identified as the most active molecule to restore the activity of MEM. Further anti-bacterial effectiveness assessment, compound 5 restored the activity of MEM against Escherichia coli, Citrobacter freundii, Proteus mirabilis and Klebsiella pneumonia, which carried resistance genes of blaNDM-1. The compound 5 was non-hemolytic, even at a concentration of 1000 µg/mL. This compound was low toxic toward mammalian cells, which was confirmed by fluorescence microscopy image and the inhibition rate of HeLa cells. The Ki value of compounds 5 against NDM-1 MBL was 5.63 ± 1.27 μM. Zinc ion sensitivity experiments showed that the inhibitory effect of compound 5 as a MBLs inhibitor was influenced by zinc ion. The results of the bactericidal kinetics displayed that compound 5 as an adjuvant assisted MEM to kill all bacteria. These data validated that this NOTA dithiocarbamate analogue is a good inhibitor of MBLs.

Developing a nanoscale drug delivery system with magnetic resonance imaging (MRI)/fluorescence imaging (FL) visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance has attracted great attentions in the area of nanomedicine. Herein, a novel permeable yolk-shell structured gadolinium-doped quantum dots nanocomposite was synthesized as a theranostic nanocarrier via an indirectly doping method. The as-prepared permeable nanoparticles with tunable color fluorescent emission, paramagnetic and accessible mesoporous channels could be developed as a novel nanomedical platform for integrated multimodal diagnosis and therapy. The hydrophilic nanocomposites exhibited tunable fluorescence as well as high longitudinal relaxivity (r 1 = 17.32 mM −1 s −1 ) in water with good colloidal stability. In vivo animal experiments further verified CSSP could achieve FL/MRI dual modality imaging. The widely used antineoplastic anthracycline drug doxorubicin (DOX) was absorbed into the permeable nanospheres with 95.3% loading efficiency and released in a pH-sensitive pattern. In vitro cancer cell cytotoxicity tests verified that the DOX-loaded nanocomposites had enhanced cytotoxicity compared with free DOX at the same concentration. The as-prepared nanocomposites present great potential as MRI/FL-visible nanoscale drug carrier to realize imaging-guided personalized therapy.

To evaluate computed tomography (CT) features and establish a predictive model for the clinical diagnosis and prognosis of tracheal adenoid cystic carcinoma (ACC).From January 2010 to December 2018, 82 patients with tracheal tumors, including 46 patients with ACC confirmed by surgery and histopathology, were enrolled in this study. These patients' clinicopathologic information, CT features and survival outcomes were recorded and analyzed. Independent predictors of diagnosis and prognosis of tracheal ACC were determined by both univariate and multivariate analyses.Compared with tracheal non-ACC patients, univariate analysis showed that ACC patients were more likely to have extensive longitudinal length (p0.001) and to appear as annular wall thickening (p = 0.001), transmural growth (p = 0.036), poorly defined border (p = 0.003) and mild enhancement (p = 0.001). Multivariate logistic analysis showed that longitudinal length and enhancement degree were independent predictors of tracheal ACC. The 3-year and 5-year disease-free survival (DFS) were 75.7 % and 64.5 %, respectively. Longitudinal length (≥ 34 mm), transverse length (≥ 20 mm) and transmural growth were associated with poor DFS in univariate analysis. After multivariate adjustment, only transverse length (≥ 20 mm) was an adverse prognostic factor for DFS (hazard ratio = 4.594, 95 % confidence interval = 1.240-17.017; p = 0.022).CT longitudinal length and enhancement degree of tumors showed satisfactory discrimination for tracheal ACC. Excessive CT transverse length might be an unfavorable indicator for ACC recurrence and could be helpful for predicting the survival outcomes of ACC at the initial diagnosis.

Summary Purpose The inhibition of Mus81, a critical DNA repair gene, is recently related to the chemosensitivity of several human cancer cells such as hepatocellular carcinoma (HCC) cells. However, the role of Mus81 knockdown in chemotherapy response of colon cancer cells remains largely unknown. Methods and materials The effects of Mus81 knockdown by lentivirus-mediated short hairpin RNA in sensitivity of HCT116 and LS180 colon cancer cell lines to four therapeutic drugs, including cisplatin (CDDP), were evaluated by MTT assay as well as a mouse model. Apoptosis and cell cycle distribution of HCT116 cell line was detected by flow cytometric analysis. Western blot was also employed to determine the expression of CHK1 pathway and apoptosis-related proteins in HCT116 cells and the xenograft mouse tumors. Results Mus81 knockdown could significantly improve the chemosensitivity of colon cancer cells in vitro and in vivo , especially to CDDP. Mus81 knockdown also induced S phase arrest and elevated apoptosis in CDDP treated HCT116 cells through activating CHK1/CDC25A/CDK2 and CHK1/p53/Bax pathways, while these effects could be counteracted by CHK1 inhibition. Conclusion Mus81 knockdown improves the chemosensitivity of colon cancer cells by inducing S phase arrest and promoting apoptosis through activating CHK1 pathway.

Necroptosis is programmed necrosis, a process which has been studied for over a decade. The most common accepted mechanism is through the RIP1-RIP3-MLKL axis to regulate necroptotic cell death. As a result of previous studies on necroptosis, positive regulation for promoting necroptosis such as HSP90 stabilization and hyperactivation of TAK1 on RIP1 is clear. Similarly, the negative regulation of necroptosis, such as through caspase 8, c-FLIP, CHIP, MK2, PELI1, ABIN-1, is also clear. Therefore, the promise of corresponding applications in treating diseases becomes hopeful. Studies have shown that necroptosis is involved in the development of many diseases, such as ischemic injury diseases in various organs, neurodegenerative diseases, infectious diseases, and cancer. Given these results, drugs that inhibit or trigger necroptosis can be discovered to treat diseases. In this review, we briefly introduce up to date concepts concerning the mechanism of necroptosis, the diseases that involve necroptosis, and the drugs that can be applied to treat such diseases.

ObjectiveThis study aims to investigate the association of serum vitamin D (VD) levels with the severity of liver fibrosis (LF) in post Kasai's portoenterostomy biliary atresia (PKBA) patients living with their native liver.MethodsIn this cross-sectional study, carried out in a tertiary Children's Hospital in Taipei, Taiwan, PKBA patients living with their native liver were enrolled. Liver biochemistry data, serum 25-hydroxyvitamin D (25-OHVD), acoustic radiation force impulse (ARFI), and scores of Pediatric Quality of Life questionnaire (PedsQL) were collected.ResultsAll the enrolled 33 PKBA patients (36.4% males), aged 1-23 years, possessed 25-OHVD less than 30ng/ml. An inverse correlation was detected between serum 25-OHVD and ARFI (r2 = 0.175; p = 0.024). We selected a cutoff value of 23ng/mL to divide PKBA patients into two groups, as the p-value was the most significant at this point when comparing the median ARFI of two groups (p = 0.003). Ten (30.3%) had 25-OHVD≥23ng/ml (HVD group), whereas 23(69.7%) had 25-OHVDConclusionVD levels are inversely associated with severity of LF in PKBA patients with native liver.

Contralateral haematoma is an infrequent but severe complication of decompressive craniectomy for head trauma.A retrospective study was performed of patients developing this complication after decompressive craniectomy for head trauma in the institute. Demographics, mechanism of trauma, time interval between trauma and first operation, time interval between first operation and onset of contralateral haematoma and patients' outcomes were recorded for further analysis.Fifteen patients developed this complication in the study; most had epidural haematomas, which appeared within the first 12 hours after decompressive craniectomy in 13 patients, including three haematomas that developed during surgical decompression. Contralateral cranial fracture is a major risk factor for this condition. Only one patient recovered to mild disability. All remaining patients had poor outcomes, with Glasgow coma scale scores ≤3, except for one patient who was lost to follow-up. A literature review of similar studies including 36 patients revealed similar characteristics.Contralateral haematoma secondary to surgical decompression in head trauma can lead to a poor outcome. The prompt detection and removal of the haematoma are keys to management and routine recurrent computed tomography is recommended after the first operation.

Methyl methansulfonate and UV sensitive gene clone 81 (Mus81) is a critical DNA repair gene that has been implicated in development of several cancers including hepatocellular carcinoma (HCC). However, whether Mus81 can affect proliferation and survival of HCC remains unknown. In the present study, we demonstrated that the knockdown of Mus81 was associated with suppressed proliferation and elevated apoptosis of HCC cells in vitro and in vivo. Multilayered screenings, including DNA microarray, high content screen, and real-time PCR validation, identified STC2 as a proliferation-facilitating gene significantly down-regulated in HCC cells upon Mus81 knockdown. STC2 expression was also closely correlated to Mus81 expression in HCC tissues. More importantly, the restoration of STC2 expression recovered the compromised cell proliferation and survival in Mus81 depleted HCC cells. Furthermore, Mus81 knockdown was associated with the activation of APAF1, APC, and PTEN pathways and concurrent inhibition of MAPK pathway through decreasing STC2 expression. In conclusion, Mus81 knockdown suppresses proliferation and survival of HCC cells likely by downregulating STC2 expression, implicating Mus81 as a therapeutic target for HCC.

Low natural killer (NK) cell counts in peripheral blood adversely affect clinical outcome of patients with follicular lymphoma

Host immunity and tumor microenvironment significantly influence follicular lymphoma (FL) outcomes. Lymphopenia has been identified as a negative prognostic factor for FL. However, there is limited data regarding prognostic value of peripheral blood T lymphocyte subsets, especially absolute CD4

To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats.A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method.Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P0.01), while the contents of plasma Ach, arterial NOS and cGMP were markedly down-regulated (P0.01). Following 7 days' acupuncture interventions, the increased blood pressure was down-regulated in the no-needle-manipulation, twirling-reinforcing needling and twirling-reducing needling groups (P0.05, P0.01); and the decreased Ach and NOS in the 3 treatment groups, and cGMP levels in the twirling-reinforcing and twirling-reducing needling groups were remarkably up-regulated (P0.01, P0.05). No significant change of arterial cGMP content was found in the no-needle-manipulation group (P0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P0.05, P0.01).The twirling-reducing needling of acupuncture has a significant anti-hypertensive effect in stress hypertension rats, which may be associated with its effects in raising blood Ach, and arterial NOS and cGMP levels.

Background: Menkes disease (MD) is a disorder of copper metabolism due to ATP7A gene mutation that leads to severe copper deficiency. Deformed blood vessels can be found in many parts of the body, and intracranial hematoma is generally reported. Methods: We report a Taiwanese boy with MD who had recurrent spontaneous subserosal hematoma of ileum presenting as intestinal obstruction, with the 2 episodes 23 months apart. The patient returned to the usual physical status after surgical removal of the hematoma. Results: The defective copper metabolism causes dysfunction of a plenty of copper-dependent enzymes, giving rise to unique kinky hair appearance, progressive neurodegeneration, and connective tissue abnormalities. To our knowledge, this is the first report on recurrent subserosal hemorrhage of intestine in MD. Conclusion: Owing to the fragile structure of blood vessels, subserosal hematoma should be considered when patients with MD having intestinal obstruction.

To evaluate the effects of red clover isoflavones on the proliferation and apoptosis of human benign prostatic hyperplasia (BPH) stromal cells.We treated human prostate stromal cells with red clover isoflavones at the concentration of 12.5, 25, 50 and 100 microg/ml, and established a PBS blank control, a dimethyl sulphoxide (DMSO) negative control and four finasteride positive control groups (at the concentration of 12.5, 25.0, 50.0 and 100.0 microg/ml). We determined the effects of different concentrations of red clover isoflavones on the proliferation of the cells by MTT assay and on their apoptosis by Annexin V/PI double staining flow cytometry.Red clover isoflavones inhibited the proliferation of the BPH stromal cells by 18.86% at 25.0 microg/ml, compared with 5.17% in the blank control group (P0.05), and more obviously at a higher concentration. At 50.0 microg/ml, red clover isoflavones exhibited a weaker inhibitory effect than finasteride (28% vs 69.88% , P0.05). Annexin V/PI double staining flow cytometry showed that red clover isoflavones at 25.0 microg/ml induced the apoptosis of the prostate stromal cells by (18.54 +/- 2.5)%, with significant differences from the negative control and blank control (P0.01).Red clover isoflavones can inhibit the proliferation and promote the apoptosis of human BPH stromal cells.

The effect of phosphorylation on the binding of protein 4.1 to erythrocyte inside-out vesicles was investigated. Protein 4.1 was phosphorylated with casein kinase A, protein kinase C, and cAMP-dependent protein kinase. An analysis of the phosphopeptides generated by alpha-chymotryptic and tryptic digestion indicates these kinases phosphorylate similar as well as distinct domains within protein 4.1. All three enzymes catalyze the phosphorylation to varying degrees of the 46-, 16-, and 8-10-kDa fragments derived from limited chymotryptic cleavage. In addition, casein kinase A phosphorylates a 24-kDa domain, whereas protein kinase C phosphorylates a 30-kDa domain. Protein 4.1 phosphorylated by casein kinase A and protein kinase C, but not cAMP-dependent protein kinase, exhibits a reduced binding to KI-extracted inside-out vesicles. On the other hand, phosphorylation of inside-out vesicles by casein kinase A does not affect their ability to bind protein 4.1. The inside-out vesicles, however, inhibit the phosphorylation of protein 4.1 by casein kinase A and protein kinase C, but not by cAMP-dependent protein kinase. These results suggest that casein kinase A and protein kinase C may modulate the binding of protein 4.1 to the membrane by phosphorylation of specific domains of the cytoskeletal protein. Since the 30-kDa domain has been suggested as a membrane-binding site, that phosphorylation by protein kinase C reduces the binding of protein 4.1 to inside-out vesicles is perhaps not surprising. On the other hand, the role of the casein kinase A substrate 24-kDa domain in membrane binding has not been established and needs to be examined.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously shown that 2,3-diphosphoglycerate (2,3-DPG) inhibits the phosphorylation of erythrocyte membrane cytoskeletal proteins by endogenous casein kinases. Here, we report that 2,3-DPG stimulates the phosphorylation of protein 4.1 by protein kinase C. Studies with red cell membrane preparations showed that while the phosphorylation of most of the membrane proteins by endogenous membrane-bound kinases and purified kinase C was inhibited by 2,3-DPG, the phosphorylation of protein 4.1 was slightly enhanced by the metabolite. The effect of 2,3-DPG was further examined using purified protein 4.1 preparations. Our results indicate that 2,3-DPG stimulates both the rate and the extent of phosphorylation of purified protein 4.1 by kinase C. The amount of phosphate incorporated was found to double to 2 mol of phosphate per mole of protein 4.1 in the presence of 10 m m 2,3-DPG. The increase in phosphorylation was distributed over all phosphorylation sites as revealed by an analysis of the labeling patterns of phosphopeptides resolved by high performance liquid chromatography, but a significantly higher incorporation was detected in two of the phosphopeptides. The stimulatory effect of 2,3-DPG on the phosphorylation of protein 4.1 was observed only with kinase C. Phosphorylation by the cytosolic erythrocyte casein kinase and the cyclic AMP-dependent protein kinase was inhibited by 2,3-DPG. Moreover, the stimulatory effect of 2,3-DPG seemed to be unique to the phosphorylation of protein 4.1 since a similar effect had not been observed with other protein kinase C substrates. Our results suggest that 2,3-DPG may play an important role in the regulation of cytoskeletal interactions.