OBJECTIVETo investigate the effects of progesterone and progestin on the expressions of regulated on activation, normal T cell expressed and secreted (RANTES) in eutopic endometrium from patients with endometriosis.

METHODSWe collected the samples of endometrium from patients with endometriosis before operation or after insertion of levenorgestrel releasing intrauterine system (LNG-IUS), administration of oral medroxyprogesterone (MPA), or injection of gonadotrophic hormone releasing hormone agonist (GnRHa). Reverse transcription-polymerase chain raction was used to assay the expression of RANTES mRNA. On the other hand, progesterone (Po) and tumor necrosis factor-alpha (TNFalpha) of different concentrations and different manners were used to treat cultured cells in vitro. RANTES secretion was evaluated in the culture medium using ELISA. In order to evaluate the effect of Po on the secretion of RANTES under stimulation of TNFalpha, the cells were cultured in medium containing 100 U/ml TNFalpha and Po of different concentrations for 24 hours. After the pretreatment of Po for 48 hours at different concentrations, TNFalpha (100 U/ml, 16 h) was added to observe whether Po inhibits RANTES or not.

RESULTSThe expression of RANTES mRNA in eutopic endometrium of patients with endometriosis was significantly higher than in control group (28.0 +/- 9.0 vs. 22.0 +/- 5.6, P < 0.05). Following the exposures to LNG-IUS (24.0 +/- 4.2 vs. 25.9 +/- 4.2, P > 0.05) or GnRHa (23.0 +/- 12.9 vs. 26.9 +/- 5.2, P > 0.05), the expression of RANTES mRNA had no change. MPA significantly increased the expression of RANTES mRNA (42.6 +/- 3.1 vs. 24.3 +/- 5.7, P < 0.05). Po itself had no significant effect on the secretion of RANTES. Stimulated by Po and TNFalpha at the same time, the secretion of RANTES significantly increased. After pretreatment with Po for 48 hours, the reaction of RANTES to the stimulating effect of TNFalpha was down-regulated.

CONCLUSIONThe eutopic endometrium of patients with endometriosis has high chemotactic activity. It may be feasible to prevent and treat endometriosis with progestins.

Cells, Cultured ; Chemokine CCL5 ; biosynthesis ; Endometriosis ; drug therapy ; metabolism ; Endometrium ; drug effects ; metabolism ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Intrauterine Devices, Medicated ; Levonorgestrel ; therapeutic use ; Medroxyprogesterone ; therapeutic use ; Progesterone ; pharmacology ; therapeutic use ; Progestins ; therapeutic use ; Transforming Growth Factor alpha ; pharmacology

OBJECTIVETo investigate the apoptosis-related mechanisms of levenorgestrel-releasing intrauterine system (LNG-IUS), oral medroxyprogesterone (MPA), and injective gonadotrophic hormone releasing hormone agonist (GnRHa) on eutopic endometrium of patients with endometriosis. Methods We collected the samples of endometrium from patients with endometriosis before operation and after insertion of LNG-IUS, administration of oral MPA, or injection of GnRHa. The ultrastructure of endometria was observed and compared by electron microscopy. Apoptotic cells were assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labeling (TUNEL) assay, and the expressions of Bax, Fas, and Fas-L mRNA were determined by semi-quantitative reverse transcription-polymerase chain raction. Results After have been exposured to LNG-IUS, the apoptotic rate of endometrial epithelial cells and stromal cells increased from (24. 4 +/- 35.0)% to (51.0 +/- 37.8)% (P = 0.027) and (35.3 +/- 30.2)% to (76.4 +/- 11.2)% (P = 0.008), respectively. The degree of apoptosis under transmission electron microscopy was in an order of GnRHa > LNG-IUS > MPA. The expression of Fas-L mRNA in eutopic endometrium of patients with endometriosis was significantly higher than that of the normal control (P < 0.05). The expressions of three apoptosis-related proteins had no significant difference.

CONCLUSIONMedical treatments can increase the apoptosis of eutopic endometrial cells, and such effect was strongest in GnRHa and relatively weaker in LNG-IUS and MPA.

Apoptosis ; Endometriosis ; drug therapy ; pathology ; Endometrium ; drug effects ; pathology ; ultrastructure ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Intrauterine Devices, Medicated ; Levonorgestrel ; therapeutic use ; Medroxyprogesterone ; therapeutic use

Objective To assess the safety and efficacy of intra-arterial chemotherapy (IAC) for the treatment of young infants (≤ 6 months) with retinoblastoma (RB).Methods Together 21 (24 eyes) young infants (≤6 months) with RB who received IAC were included from January 2013 to February 2017 in this study and the clinical data were retrospectively analyzed.According to the international stages for intraocular retinoblastoma,stage B appeared in 4 eyes,stage D in 13 eyes,and stage E in 7 eyes.And there were two kinds of administration for chemotherapy,including perfusion chemotherapy of melphalan (≤ 0.5 mg · kg-1) combined carboplatin (20 mg) on the first and third IAC procedures,and melphalan (≤ 0.5 mg · kg-1) combined with topotecan (0.5-1.0 mg) on the second and fourth IAC procedures,and the dose of melphalan was appropriately adjusted according to the tumor changes and the response of the child after the previous IAC.Then main outcome measures include successful rate for procedures,ocular preservation rate,local and systemic complications and the time and dose of radiation exposure during IAC were evaluated.Results Of the 70 IAC procedures performed on 24 eyes,69 procedures (98.6％) were successful,and 1 was failed due to ophthalmic spasm.IAC ranged from 2 to 4 cycles with mean 3.3 cycles.After IAC procedures,17 eyes presented fish-like changes or calcification or scar formation,and the overall ocular preservation rate was 70.8％,and the other 7 eyes (29.2％) underwent enucleation of the eyeballs due to fundus hemorrhage in 3 eyes and extensive vitreous implantation in 4 eyes.Postoperative adverse reactions included eyelid oedema in 8 patients,fundus hemorrhage in 3 eyes,ocular arteriospasm in 1 patients and bone marrow suppression in 9 patients.The mean irradiation time was 3.2-32.4 (6.3 ± 1.2) min for one IAC procedure and the mean irradiation dose was 5-153 (51.9 ±9.2)mGy.The cumulative irradiation time was 6.6-53.1 (19.2 ±0.9)min for each patient of IAC cycles and the cumulative irradiation dose was 41-281 (157.3 ± 13.1) mGy.Conclusion IAC is safe and effective for the treatment of young infants (≤≤ 6 months) with RB,and the irradiation dose in IAC is lower than the threshold dose that can cruise lens tissue reactions.

OBJECTIVETo investigate the kinetic expression and alteration of nuclear transcription factor-kappa B (NF-kappaB) and its gene in hepatocellular carcinoma (HCC) development.

METHODSA hepatoma model was established with N-(2-fluorenyl) acetamide (2-FAA) using male SD rats. Morphological changes and dynamic alterations of NF-kappaB and NF-kappaB mRNA of the rat livers at different stages of HCC development were observed by pathological examinations. The liver specimens from HCC patients were collected by self-control method. The expression of NF-kappaB was quantitatively analyzed by ELISA.

RESULTSHepatocytes showed vacuole-like denaturation, atypical hyperplasia, and transformation into highly differentiated cancerous hepatocytes with increasing tendencies of liver NF-kappaB and NF-kappaB mRNA expressions. The NF-kappaB positive material was granule-like and stained brown, with dot-nest-like staining localized in the nuclei and cytoplasm of HCC cells, but only in the cytoplasm of the cells of park cancer tissues. Its expression in HCC cells was stronger than that in their surrounding tissues (chi2 = 13.1, P less than 0.01). No positive relationship was found between NF-kappaB expression and histological grades, the number of tumors, or size of the tumors.

CONCLUSIONThe expression of NF-kappaB and its gene are associated with the development of HCC. To inhibit the expression may be useful to HCC therapy.

Adult ; Aged ; Animals ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms, Experimental ; metabolism ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley

The effects of cardiomyocyte grafting on left ventricular (LV) remodeling and function in rats with chronic myocardial infarction were evaluated using high-frequency ultrasound. Chronic myocardial infarction was induced in 50 Wister rats by ligating the left anterior descending artery. They were randomized into two groups: a trial group that received neonatal rat cardiomyocyte trans- plantation (n=25) and a control group which were given intramyocardial injection of culture medium (n=25). The left ventricular (LV) geometry and function were evaluated by high-frequency ultrasound before and 4 weeks after the cell transplantation. After the final evaluation, all rats were sacrificed for histological study. The results showed that 4 weeks after the cell transplantation, as compared with the control group, the LV end-systolic dimension, end-diastolic dimension, end-systolic volume and end-diastolic volume were significantly decreased and the LV anterior wall end-diastolic thickness, LV ejection fraction and fractional shortening were significantly increased in the trial group (P<0.01). Histological study showed that transplanted neonatal rat cardiomyocytes were found in all host hearts and identified by Brdu staining. It was suggested that transplantation of neonatal rat cardiomyocytes can reverse cardiac remodeling and improve heart function in chronic myocardial infarction rats. High-frequency ultrasound can be used as a reliable technique for the non-invasive evaluation of the effect of cardiomyocyte transplantation.

BACKGROUNDThin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endometrial thickness (EMT). The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium.

METHODSRelevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student's t-test and the Chi-square test.

RESULTSAt the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients (92.1%). Effectiveness of treatment was significantly associated with maximal pretreatment EMT (P = 0.017) and treatment duration (P = 0.004). The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh (P = 0.005) and frozen-thawed (P = 0.000) embryo transfer cycles.

CONCLUSIONSThinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful (i.e., achieves an EMT ≥8 mm) are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.

Endometrium ; drug effects ; Estrogens ; therapeutic use ; Female ; Humans ; Infertility, Female ; drug therapy ; therapy ; Male ; Pregnancy ; Pregnancy Rate ; Retrospective Studies

Objective: To establish a purge and trap-gas chromatography-mass spectrometry method based on soil analysis model for the determination of six benzene homologues (benzene, toluene, ethylbenzene, m-xylene, p-xylene and o-xylene) in human blood. Methods: From September 2020 to May 2021, diatomite was used as a dispersant to add 2.0 ml blood sample and fully mixed. The sample was directly injected into the purging and collecting bottle after purging. The gas chromatography column was used for separation. The retention time locking was used for qualitative analysis and the selected ion scanning mode (SIM) was used for detection. The detection limit and recovery rate of the method were analyzed. Results: The linear range of the method for the determination of six benzene homologues in human blood was 0.02-10.00 ng/ml, the correlation coefficient was 0.9927-0.9968, the detection limit was 0.006-0.016 ng/ml, the recovery rate of sample spiking was 84.39%-102.41%, and the precision of the method was 3.06%-6.90%. Conclusion: Purge and trap-gas chromatography-mass spectrometry can simultaneously determine the contents of six benzene homologues in human blood. The pretreatment method is simple, time-saving, and the method has low detection limit, which provides a scientific basis for the detection of benzene homologues in human body.
Humans ; Benzene/analysis* ; Gas Chromatography-Mass Spectrometry/methods* ; Xylenes/analysis* ; Benzene Derivatives/analysis* ; Toluene/analysis*

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.