A multicentre, randomized, double-blind, placebo-controlled trial of topical oestradiol gel for endometrial regeneration after induced abortion.

STUDY QUESTION: Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion? SUMMARY ANSWER: Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects. WHAT IS KNOWN ALREADY: Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited. STUDY DESIGN, SIZE, DURATION: We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P > 0.05). LIMITATIONS, REASONS FOR CAUTION: Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gestation improves endometrial regeneration and growth, thereby potentially increasing the chances of a successful subsequent pregnancy. Clinical application of these findings may improve endometrial health management practices and provide a perspective on fertility treatment and women's reproductive health. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant (FW-HKKT2021111501900) from Jianmin Pharmaceutical Group Co., Ltd (JMPG), Wuhan, Hubei, China. Both the oestradiol gel and the simulant were provided by JMPG. The funding source had no role in the study. X.Y.L. reports JMPG grant funding paid to their institutions. All other authors declare no competing interests. TRIAL REGISTRATION NUMBER: CHiCTR2100053565. TRIAL REGISTRATION DATE: 24 November 2021. DATE OF FIRST PATIENT'S ENROLMENT: 9 March 2022.

Can Optical Surface Imaging Replace Non-coplanar Cone-beam Computed Tomography for Non-coplanar Set-up Verification in Single-isocentre Non-coplanar Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Single and Multiple Brain Metastases?

AIMS: To conduct a direct comparison regarding the non-coplanar positioning accuracy between the optical surface imaging system Catalyst HDTM and non-coplanar cone-beam computed tomography (NC-CBCT) in intracranial single-isocentre non-coplanar stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT). MATERIALS AND METHODS: Twenty patients with between one and five brain metastases who underwent single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) SRS or HSRT were enrolled in this study. For each non-zero couch angle, both Catalyst HDTM and NC-CBCT were used for set-up verification prior to beam delivery. The set-up error reported by Catalyst HDTM was compared with the set-up error derived from NC-CBCT, which was defined as the gold standard. Additionally, the dose delivery accuracy of each non-coplanar field after using Catalyst HDTM and NC-CBCT for set-up correction was measured with SRS MapCHECKTM. RESULTS: The median set-up error differences (absolute values) between the two positioning methods were 0.30 mm, 0.40 mm, 0.50 mm, 0.15°, 0.10° and 0.10° in the vertical, longitudinal, lateral, yaw, pitch and roll directions, respectively. The largest absolute set-up error differences regarding translation and rotation were 1.5 mm and 1.1°, which occurred in the longitudinal and yaw directions, respectively. Only 35.71% of the pairs of measurements were within the tolerance of 0.5 mm and 0.5° simultaneously. In addition, the non-coplanar field with NC-CBCT correction yielded a higher gamma passing rate than that with Catalyst HDTM correction (P < 0.05), especially for evaluation criteria of 1%/1 mm with a median increase of 12.8%. CONCLUSIONS: Catalyst HDTM may not replace NC-CBCT for non-coplanar set-up corrections in single-isocentre NC-VMAT SRS and HSRT for single and multiple brain metastases. The potential role of Catalyst HDTM in intracranial SRS/HSRT needs to be further studied in the future.

[Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease].

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

[The effect of welding ultraviolet on the antioxidant function and DNA of workers].

Objective: To explore the skin damage, oxidative damage and DNA damage of welding workers caused by ultra violet. Methods: From 1 May to 30 June 2017, 125 welding workers were selected as the contact group, which was divided into 2, 4, 6, 8 and 10-year-working age groups with 25 workers in each group and 25 healthy volunteers as the control group. The workers in the contact group were investigated with questionnaires on the distribution and wearing of protective equipment; the subjects in the two groups were examined in dermatology, and the peripheral blood was collected to detect the total antioxidant capacity (T-AOC) and DNA damage of mononuclear cells, and the influence of ultraviolet on the above indexes was analyzed. Results: The distribution rates of welding mask, dust mask and goggles were 100.0% (125/125) , 96.0% (120/125) , 98.4% (123/125) , respectively, and the distribution rates of welding gloves were 64.8% (81/125) ; the wearing rates of welding mask and goggles were 100.0% (125/125) , 90.4% (113/125) , and the wearing rates of dust mask and welding gloves were 89.6% (112/125) and 64.0% (80/125) , respectively. The acute skin injuries such as hand and face peeling and skin pruritus were serious in the 2-year-working age group, and the chronic skin injuries such as insensitive and numbness and verrucous vegetations were the main manifestations in the 10-year-working age group. Compared with the control group, T-AOC in peripheral blood of workers exposed to 6, 8 and 10 years decreased significantly, and DNA content in comet tail of workers exposed to various working years increased significantly (P<0.05) , while DNA content in comet tail increased with working years (F=1501.130, P<0.05) . Conclusion: UV welding can cause skin damage, reduce the antioxidant capacity of the body, and increase DNA damage with the increase of working age.

Long non-coding RNA OIP5-AS1 plays an oncogenic role in ovarian cancer through targeting miR-324-3p/NFIB axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been found to exert specific functions in the progression of ovarian cancer (OC), except for lncRNA-OIP5-AS1. In this study, we aim at exploring the molecular mechanisms of OIP5-AS1 in OC. PATIENTS AND METHODS: The expression levels of OIP5-AS1, miR-324-3p, and NFIB in OC tissues and OC cell lines were explored by qRT-PCR assay. The OC cell vitality was examined by CCK-8 and transwell assay. The protein expression level of NFIB was measured by Western blot analysis. The correlation between OIP5-AS1, miR-324-3p, and NFIB was appraised by Dual-Luciferase reporter assay. RESULTS: OIP5-AS1 and NFIB were validated to be upregulated in both OC tissues and OC cell lines. Inversely, miR-324-3p downregulation was found in OC tissues and OC cell lines. Functionally, OIP5-AS1 knockdown and miR-324-3p overexpression restrained SKOV3 cell viability, invasion, and migration. Our results verified that OIP5-AS1 inhibited the expression of miR-324-3p in OC. Moreover, miR-324-3p directly targets NFIB. Besides that, NFIB silencing restrained the progression of SKOV3 cells. CONCLUSIONS: The present study clarified that OIP5-AS1 accelerated OC progression by sponging miR-324-3p and upregulating NFIB. OIP5-AS1 can be a possible therapeutic target for the treatment of OC.

I/D polymorphism of ACE and risk of diabetes-related end-stage renal disease: a systematic review and meta-analysis.

OBJECTIVE: We conducted a meta-analysis on exploring the correlation between I/D polymorphism of ACE and risk of diabetes mellitus-related end-stage renal disease. MATERIALS AND METHODS: Researches on the correlation between I/D polymorphism of ACE and the risk of diabetes-related end-stage renal disease were searched in the three online databases (PubMed, Embase, and Cochrane Library). Citations of related researches were manually examined and enrolled. This study systematically searched relative literature for cohort studies or case-control studies published in the English language until December 1, 2018. Researches containing odds ratio (OR) and 95% confidence interval (CI) calculated based on the correlation between I/D polymorphism of ACE and the risk of diabetes-related end-stage renal disease were enrolled. The included data were weighted by an inverse variance and then analyzed by a fixed or random effects model. Researches met the inclusion criteria were extracted for relevant data and subjected to a heterogeneity test. The effect size was calculated by STATA 12.0 software for meta-analysis. RESULTS: A total of 15 articles including 1199 cases of diabetes-related end-stage renal disease and 2939 cases of controls were enrolled. I/D polymorphism of ACE remarkably increased the risk of diabetes-related end-stage renal disease. In the subgroup analysis by ethnicity, a significant difference in risk of diabetes-related ESRD was only detected in the Asian population with I/D polymorphism of ACE. However, no significant difference in disease risk was found in the Caucasian population. CONCLUSIONS: This meta-analysis suggested that I/D polymorphism of ACE can markedly increase the incidence of diabetes-related end-stage renal disease, especially in Asian populations.

[The evaluation of severity and treatment for OSAHS by acoustic pharyngometry which in different postures].

Objective: To investigate the optimal position in application of acoustic pharyngometry to detect the pharyngeal condition and to assess its therapeutic effect on obstructive sleep apnea hypopnea syndrome(OSAHS). Method: Eight adult males were assigned to the normal group, and 57 male patients with OSAHS diagnosed by polysomnograhy(PSG) were assigned to the snoring group. Of the snoring group, 11 patients who were diagnosed severe OSAHS underwent low-temperature plasma uvulopaltopharyngoplasty(UPPP) and coblationchanneling of the tongue(CCT), were assigned to the operation subgroup; 8 patients underwent continuous positive airway pressure(CPAP), which was assigned to the CPAP subgroup. And remainders underwent conservative treatment, including weight loss and position change. Acoustic pharyngometry (three positions including sitting position, supine position and lateral position) and PSG exam were performed in all participants. Additionally, acoustic pharyngometry under three positions was conducted again in patients in the operation and CPAP subgroups three months after treatment. Result: The minimum cross-sectional area was negatively associated with both AHI and the percentage of time with oxygen saturation below 90%(SIT90)( P<0.01). The correlation coefficient of the minimum crosssectional area insupine position with AHI and SIT90 were r=-0.569,r=-0.478, respectively. Under supine position, the minimum crosssectional area was negatively correlated with body mass index(BMI)(r=-0.265, P=0.033), and the minimum crosssectional area was negatively associated with neck circumference(r=-0.309, P=0.012). The minimum cross-sectional area was significantly increased after treatment of OSAHS(both operation and CPAP), which was statistically different before and after treatment compared to the control group(P<0.01). Conclusion: ①The minimum cross-sectional area is significantly correlated with AHI and SIT90, respectively. The acoustic pharyngometry can be used to screen OSAHS patients. ②In this study, the minimum cross-sectional area under supine position is significantly smaller than that under sitting position. In addition, the minimum cross-sectional area under supine position harbored a better correlation with AHI and SIT90, which could better reflect the narrowness of pharyngeal cavity during sleep. ③Acoustic pharyngometry could be a simple, rapid and non-invasive technique that can objectively evaluate the efficacy of surgical and CPAP methods, and provided a more favorable basis for future clinical work..

Mitochondria-mediated disturbance of fatty acid metabolism in proximal tubule epithelial cells leads to renal interstitial fibrosis.

The article "Mitochondria-mediated disturbance of fatty acid metabolism in proximal tubule epithelial cells leads to renal interstitial fibrosis" by W. Shen, X.-X. Jiang, Y.-W. Li, Q. He, published in Eur Rev Med Pharmacol Sci 2018; 22 (3): 810-819 has been withdrawn.

Mitochondria-mediated disturbance of fatty acid metabolism in proximal tubule epithelial cells leads to renal interstitial fibrosis.

OBJECTIVE: To investigate the role of mitochondria-mediated fatty acid metabolism in proximal tubule cells in renal interstitial fibrosis. MATERIALS AND METHODS: Intraperitoneal injection of folate was performed to induce renal interstitial fibrosis in mice. Polymerase chain reaction (PCR) was used to detect the expression of cytochrome c oxidase subunit IV (COX4IL) and phosphoenolpyruvate carboxykinase 1 (PCK1) in samples. Electron microscope was used to detect the activity of mitochondria. Serum creatinine and urea nitrogen were chosen as evaluation criteria for renal function. Western-blotting was used to detect protein expression of cells. Immunohistochemistry was used to test renal structure and deposition of collagen. RESULTS: In renal interstitial fibrosis, mitochondria mediated the dysfunction and the promotion of tubulointerstitial fatty acid metabolism. Besides, it could also reduce renal interstitial fibrosis and alleviate the fatty acid metabolism of tubulointerstitial fibrosis. CONCLUSIONS: Mitochondrial dysfunction induced fatty acid metabolism is an important factor to promote the progress of renal interstitial fibrosis. Intervention of related targets of fatty acid metabolism is expected to become a new treatment for renal interstitial fibrosis.

High calcium to phosphorus ratio impairs growth and bone mineralization in Pekin ducklings.

Two experiments were conducted to investigate the effect of high dietary calcium (Ca) level on growth performance, Ca and phosphorus (P) metabolism, and nutrient utilization in ducklings subjected to normal and low P levels in diets. A completely randomized design was used with a factorial arrangement of 2 total dietary P levels [normal-P (0.60%) and low-P (0.45%) groups] × 4 dietary Ca levels [low-Ca (0.55%), normal-Ca (0.75%), medium-Ca (0.95%) and high-Ca (1.15%) groups)]. Compared to normal-P group, low-P group had lower (P < 0.05) final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) and reduced (P < 0.05) serum Ca and P levels, bone Ca, P, and ash content, and bone mineral density in ducklings during the starter period. Under the low-P group, birds from high-Ca group had lower (P < 0.05) final BW, ADG, ADFI, bone ash content, bone mineral density, and the utilization of energy, Ca, and P than those from low-Ca, normal-Ca, and medium-Ca groups. Our results indicate that high-Ca diet induced greater growth suppression and bone mineralization loss in ducklings fed a low-P diet. The aggravated negative effect of high dietary Ca level with a low P level might be related to the elevated serum alkaline phosphatase activity and the reduced utilization of energy, Ca, and P.

[Clinical comparison of modified laparoscopic and conventional placement of peritoneal dialysis catheters].

Objective: To explore the clinical efficacy of the modified laparoscopic placement of peritoneal dialysis catheters by nephrologists. Methods: A total of 188 patients diagnosed as end-stage renal disease (ESRD) were enrolled, who received catheter and continuous ambulatory peritoneal dialysis (CAPD) therapy from January 2011 to May 2016 in Zhejiang Provincial People's Hospital. They were divided into group A (with modified laparoscopic placement of peritoneal dialysis catheters, n=59) and group B (with conventional placement of peritoneal dialysis catheter, n=129). The demographic and clinical characteristics, past abdominal operation history, surgery time, hospital stay after operation, expenses for surgery and hospitalization, early and late complications including bleeding, pain, leakage, peritonitis and catheter displacement were observed. Results: Patients with previous abdominal surgery accounted for 11.9% in group A and 0 in group B(χ2=15.897, P<0.001). The duration of the operation was (38.9±12.8)min in group A and (64.1±12.7)min in group B(t=-6.466 6, P=0.000 0). The cost of the operation was (5 488.4±156.1) yuan in group A and (1 602.7±48.92) yuan in group B (t=257.129, P=0.000 0). Catheter displacement within one month was observed in 0 and 11.6%(χ2=7.455 3, P=0.003), pain in 15.3% and 41.9% (χ2=12.862 2, P=0.000), and catheter displacement after one month in 0 and in 16.3% (χ2=10.812 4, P=0.000) of the patients, respectively in group A and group B. The incidences of peritonitis within one month and beyond one month, leakage, bleeding and so on showed no difference between the two groups(P>0.05). Conclusions: Placement of PD catheter with laparoscope is suitable for renal failure patients with abdominal operation history and replacement PD catheter. It also has the advantages of shorter surgery time, less pain and lower incidences of catheter displacement, expanding the application of PD. However, bleeding, leakage, hernia and other complications are frequently seen.

A pooled analysis of MRI in the detection of bone marrow infiltration in patients with malignant lymphoma.

AIM: To explore the role of magnetic resonance imaging (MRI) in detecting bone marrow infiltration of malignant lymphoma through a systematic review and meta-analysis. MATERIALS AND METHODS: Studies that evaluated the diagnostic performance of MRI in detecting bone marrow infiltration of malignant lymphoma were acquired from the MEDLINE, EMBASE, Cancerlit, and Cochrane Library database, from February 1987 to May 2012. Pooled estimation and subgroup analysis data were obtained by statistical analysis. RESULTS: A total of 13 studies involving 634 patients who fulfilled all of the inclusion criteria were considered for the analysis. No publication bias was found (p = 0.70). The pooled sensitivity of MRI was 0.82 [95% confidence intervals (CI): 0.70-0.90] and the pooled specificity was 0.79 (95% CI: 0.72-0.84). Overall, positive likelihood ratios (LR+) was 3.9 (95% CI: 2.8-5.4) and negative likelihood ratios (LR-) was 0.23 (95% CI: 0.13-0.41). In patients with high pre-test probabilities, MRI enabled confirmation of bone marrow involvement; in patients with low pre-test probabilities, MRI enabled exclusion of bone marrow involvement. Worst-case-scenario (pre-test probability, 50%) post-test probabilities were 80% and 18% for positive and negative MRI results, respectively. In subgroup analysis, MRI performed with 1.5 T devices had higher pooled specificity (0.80, 95% CI: 0.71-0.88) than the MRI with ≤1 T (0.78, 95% CI: 0.71-0.85; p < 0.05). The pooled sensitivity of MRI with diffusion-weighted imaging (DWI) was 0.65 (95% CI: 0.39-0.92) and the pooled specificity was 0.83 (95% CI: 0.69-0.97). The sensitivity and specificity of MRI without DWI was 0.85 (95% CI: 0.76-0.94) and 0.79 (95% CI: 0.72-0.85), respectively. CONCLUSION: A limited number of small studies indicate that MRI can serve as a valuable tool for detecting bone marrow infiltration of malignant lymphoma. Results were most promising when performing MRI using high field strength devices. MRI with DWI is shown to be more specific than conventional MRI techniques. This deserves further investigation in future studies.

Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine produces antidepressant effects in rats: role of brain-derived neurotrophic factor.

Recent studies highlight that the brain glutamate system is involved in the etiology of depression and glutamatergic-targeting drugs are currently being explored as novel antidepressant medications. Previous studies reveal that the selective metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) produces antidepressant-like effects in behavioral despair and olfactory bulbectomy models. The current study aimed to further explore its behavioral actions in additional animal models of depression (forced swimming test (FST) and learned helplessness (LH) test) and its underlying neurobiological mechanisms. The results demonstrated that acute treatment of MPEP at 30 but not 10mg/kg significantly reduced immobility in FST without affecting locomotor activities. Sub-chronic, five-day treatment of MPEP (30 mg/kg) decreased escape failures in animals that had developed LH symptoms. This sub-chronic treatment also increased hippocampal brain-derived neurotrophic factor (BDNF) protein levels in both non-stressed and stressed animals and restored the stress-induced down-regulation of BDNF expression. Current findings provide strong evidence for further studies of MPEP as a tool to explore novel antidepressants.

Levels of PCDD/Fs, Dl-PCBs and HCB in air, soils and sediments from a city with multiple thermal-related industries in China.

The levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs) and hexachlorobenzene (HCB) were measured in various environmental compartments in Tangshan, China, which contains multiple thermal-related industries. The total toxic equivalent concentrations of these pollutants were 138 ± 87.2 fg/m(3) in air, 3.43 ± 2.88 pg/g in soils, and 1.42 ± 1.5 pg/g in sediments. The 2,3,7,8-PCDD/Fs profiles in atmospheric samples suggest that thermal-related industries are the most likely potential sources. Of the dl-PCBs, CB-77, CB-105 and CB-118 were the most abundant congeners and CB-126 was the dominant contributor to the TEQs from the dl-PCBs.

Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases.

The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.

The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis.

Interactions between inhibitors of the proteasome and histone deacetylases have been examined in human T-leukemia/lymphoma cells both in vitro and in vivo. Co-exposure of cells to bortezomib and suberoylanilide hydroxamic acid (SAHA) synergistically induces T-leukemia/lymphoma cells to undergo apoptosis, consistent with a significant increase in mitochondrial injury and caspase activation. These events are accompanied by inhibition of cyto-protective signaling pathways, including the nuclear factor (NF)-kappaB, Raf-1/mitogen-induced extracellular kinase (MEK)/extracellular signal-related kinase (ERK) and AKT pathways, and activation of stress-related cascades, including the stress-activated kinases c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK). Moreover, bortezomib in conjunction with SAHA efficiently induces apoptosis of primary T-leukemia/lymphoma cells and inhibits tumor growth in a murine xenograft model established with subcutaneous injection of Jurkat cells. Taken together, these findings confirm the synergistic anti-tumor effect of the proteasome and histone deacetylase inhibitors, and provide an insight into the future clinical applications of bortezomib-SAHA combining regimen in treating T-cell malignancies.

Voxel-based detection of white matter abnormalities in mild Alzheimer disease.

OBJECTIVE: To detect white matter abnormalities in patients with mild Alzheimer disease (AD) by diffusion tensor imaging and to determine their topographic relationship with gray matter atrophy. METHODS: Thirteen patients with mild AD and 16 normal age-matched volunteers underwent diffusion tensor imaging and three-dimensional spoiled gradient-recalled sequence scanning. Voxel-based morphometry was conducted to detect regions of gray matter atrophy in the AD group relative to the control group. Fractional anisotropy (FA) maps were processed using SPM2 to make voxel-wise comparison of anisotropy in whole brain between the two groups. The relationship between locations of abnormalities in the white and gray matter was examined. RESULTS: Significant reductions in anisotropy were found in the white matter of both medial temporal lobes, bilateral temporal stems, bilateral superior longitudinal fasciculi, bilateral internal capsules, and cerebral peduncles, as well as the white matter of left middle temporal gyrus and right superior parietal lobule, the body and genu of the corpus callosum, and the right lateral capsule in patients with AD. Although the decrease in FA was consistent with cortical volumetric reduction in both temporal lobes, the widespread involvement of bilateral superior longitudinal fasciculi was dominant in these white matter findings. CONCLUSIONS: Voxel-wise comparison of whole-brain anisotropy revealed widely distributed disintegration of white matter in mild Alzheimer disease (AD). The white matter shows a different pattern of degeneration from gray matter and may be an independent factor in the progress of AD.

WITHDRAWN: Isolation and Identification of a Multilineage Potential Mesenchymal Cell from Human Placenta.

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