Research and Analysis of Molecules such as CD28, CD45RA, CD45RO, CD38, HLA-DR, and CD57 on T Cells in Multiple Myeloma.

BACKGROUND: For many years it has been postulated that the immune system controls the progress of multiple myeloma (MM). However, the phenotypes of T cells in MM remain to be elucidated. In this study, we compared the phenotypes of T cells, which were obtained from the peripheral blood, in MM patients with those in healthy donors (HD). The expression of CCR7, CD57, CD28, HLA-DR, CD38, CD45RA, and CD45RO were assessed on T cells from MM patients and HDs using multicolor flow cytometry (MFC). METHODS: For this study, 17 newly diagnosed MM patients were selected, and 20 healthy people were selected as a control group. MFC was used to detect the markers on T cells. RESULTS: We detected significant increases in the expression levels of HLA-DR, CD38, and CD57on CD8+ T cells, significant decreases in the expression levels of CD28 and CD45RA on CD8+ T cells, and a decrease of CD4+ effec-tor T cells in MM patients, compared to the HD group. CONCLUSIONS: Our study shows that the accumulation of peripheral CD8+CD57+T cells, CD8+CD38high T cells, and CD8+HLA-DR+CD38high T cells is reflective of an ongoing antitumor T cell response and a progressive immune dysfunction in MM. During chemotherapy, the recovery of immune function can be monitored by detecting the proportion of activated molecules of T lymphocytes.

A Case of Chronic Eosinophilic Leukemia with CSF3R-Mutant Clone and Transformed to Secondary Acute Myeloid Leukemia.

BACKGROUND: Chronic eosinophilic leukemia (CEL) is a rare invasive disease characterized by non-specific cytogenetic abnormalities or elevated mother cells, poor prognosis, and a high risk of conversion to acute leukemia. METHODS: We described the data of a patient with CEL-NOS. RESULTS: This case is a CEL-NOS with four mutations in CSF3R-T618I, DNMT3A Q816, ASXL1, and IDH2. CONCLUSIONS: The patient rapidly evolves into secondary acute myeloid leukemia (AML).

Bortezomib modulated the autophagy-lysosomal pathway in a TFEB-dependent manner in multiple myeloma.

OBJECTIVE: To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment. METHODS: MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(http://gtrd.biouml.org/) website, and pathway analysis was performed. RESULTS: Bortezomib demonstrated a dose-dependent and time dependent inhibition of cell proliferation. In MM cells treated with bortezomib, LC3B, Beclin-1, TFEB, and Lamp1 exhibited upregulation in a time- and concentration-dependent manner. LysoTracker dye labeling showed an increase in lysosomes in the bortezomib-treated group. Moreover, bortezomib elevated the expression of lysosome-associated factor Lamp1. Bortezomib promoted the nuclear translocation of TFEB, leading to decreased cytoplasmic TFEB and increased nuclear TFEB. TFEB gene silencing reversed bortezomib's inhibitory effect on MM cell lines, significantly reducing autophagosome expression and lysosome numbers. Furthermore, bioinformatic analysis identified the MAPK pathway as a potential downstream target of TFEB. CONCLUSION: Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.

Therapy-related acute myeloid leukemia with CBFB/MYH11 in a patient with ovarian cancer after exposure to chemotherapy.

In patients with acute myeloid leukemia (AML), about 25%-35% of patients have a history of other hematological diseases, 10% of patients have a history of malignant tumors in other systems and have received cytotoxic treatment including chemotherapy and/or radiation, and the disease is categorized as therapy-related acute myeloid leukemia (t-AML) according to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. Two subsets of t-AML are generally recognized based on the nature of prior treatments and the characteristics of the disease. The most common type occurs after exposure to alkylating agents and/or radiation, with a latent period of 5 to 10 years. The less common type occurs after treatment with agents targeting topoisomerase II and has a shorter latent period of 1 to 5 years. The majority of these cases are associated with balanced recurrent chromosomal translocations frequently involving MLL at 11q23, RUNX1 at 21q22, or CBFB at 16q22 and morphologically resemble the features of de novo AML associated with these translocations. Here, we describe a rare case of a 48-year-old female with ovarian cancer who developed AML with CBFB/MYH11 fusion, less than two years after exposure to paclitaxel and carboplatin chemotherapy.

Live Birth Rate of Frozen-Thawed Single Blastocyst Transfer After 6 or 7 Days of Progesterone Administration in Hormone Replacement Therapy Cycles: A Propensity Score-Matched Cohort Study.

Background: Progesterone administration before transfer in hormone replacement treatment (HRT) is crucial to pregnancy outcomes in frozen-thawed blastocyst transfer (FET), but the optimal progesterone duration is inconsistent. The objective of this study was to investigate live birth rate (LBR) of different progesterone duration before blastocyst transfer in HRT-FET cycles. Method: In this retrospective cohort study, patients underwent first HRT-FET (including suppression HRT) from January 2016 to December 2019 were included. Logit-transformed propensity score matching (PSM) was performed to assess covariates. The primary outcome was live birth rate after 28 weeks' gestation. Basing on different duration of progesterone before transfer, patients were classified into P6-protocol (blastocyst transfer performed on the sixth day), or P7-protocol (blastocyst transfer performed on the seventh day). Subgroup analyses were conducted as follows: age stratification (-35, 35-38, 38-), development days of blastocyst (D5 or D6), blastocyst quality (high-quality or poor-quality), and endometrial preparation protocols (HRT or suppression HRT). Result: After case matching with propensity score methods, a total of 1,400 patients were included finally: 700 with P6-protocol and 700 with P7-protocol. Significantly higher live birth rate (38.43% versus 31.57%, respectively, P = 0.01) and clinical pregnant rate (50.43% versus 44.14%, respectively, P = 0.02) were observed in P6-protocol than those of P7-protocol. First-trimester abortion rates (18.13% versus 20.71%, P = 0.40) and ectopic pregnancy rates (2.27% versus 1.94%, P = 0.77) were similar between P6- and P7-groups. Preterm birth rate, low birth weight rate, newborn sex proportion, neonatal malformation rate were comparable between groups. Significantly higher LBRs were observed in patients with: age under 35, D5 blastocyst transfer, high-quality blastocyst transfer, and undergoing HRT cycles combined P6-protocol. Conclusion: Frozen-thawed blastocyst transfer on the sixth day of progesterone administration in first HRT cycle is related to higher live birth rate compared with transfer on the seventh day, especially among patients aged under 35, D5 blastocyst and/or high-quality blastocyst transfer.

Roles of miRNA dysregulation in the pathogenesis of multiple myeloma.

Multiple myeloma (MM) is a malignant disease of plasma cells with complex pathology, causing significant morbidity due to its end-organ destruction. The outcomes of patients with myeloma have significantly improved in the past couple of decades with the introduction of novel agents, such as proteasome inhibitors, immunomodulators, and monoclonal antibodies. However, MM remains incurable and presents considerable individual heterogeneity. MicroRNAs (miRNAs) are short, endogenous noncoding RNAs of 19-22 nucleotides that regulate gene expression at the posttranscriptional level. Numerous studies have shown that miRNA deregulation is closely related to MM pathology, including tumor initiation, progression, metastasis, prognosis, and drug response, which make the complicated miRNA network an attractive and marvelous area of investigation for novel anti-MM therapeutic approaches. Herein, we mainly summarized the current knowledge on the roles of miRNAs, which are of great significance in regulating pathological factors involved in MM progressions, such as bone marrow microenvironment, methylation, immune regulation, genomic instability, and drug resistance. Meanwhile, their potential as novel prognostic biomarkers and therapeutic targets was also discussed.

Application of chromosome microarray analysis in prenatal diagnosis.

BACKGROUND: To explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis. METHODS: The results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared. RESULTS: Abnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype (P < 0.01) and of VOUS (P < 0.01), but there was no significant difference in the detection rate of pCNV (P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes (P > 0.05), pCNV (P > 0.05) or VOUS (P > 0.05). CONCLUSIONS: The detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.

Cumulative Live Birth Rate in Patients With Thin Endometrium: A Real-World Single-Center Experience.

Background: Studies have shown that patients with a thin endometrial thickness (EMT < 7 or 8 mm) during IVF/ICSI tend to have adverse pregnancy outcomes, and this has caused much anxiety to both patients and physicians when confronted with a thin EMT. Method: From January 2015 to December 2018, patients with a thin EMT < 7 mm on the day of hCG administration during their first GnRH agonist IVF/ICSI cycle were included. According to the hysteroscopy results, patients were classified into totally normal (Group A), normal with a specific abnormality (Group B), and adhesion before transfer (Group C). Result: For the 245 patients included, approximately 60% of the thin EMT cases were the result of an intrauterine operation. CLBR was 35.45% (67/189) in this group of patients. In regard to CLBR, there were significant differences among these three uterus condition groups irrespective of the number of oocytes retrieved (28.57 vs. 10.00 vs. 4.76%, P = 0.12 in oocyte ≤5; 61.36 vs. 44.67 vs. 23.63%, P = 0.00 in oocyte >5). In binary logistic regression analysis, age (OR = 0.09, P = 0.03), number of embryos available (OR = 1.71, P = 0.00), and uterine condition (OR = 6.77, P = 0.00 for group A; OR = 2.55, P = 0.04 for group B; Reference = group C), were significantly associated with CLBR. However, EMT and endometrial pattern had no impact on CLBR. Conclusion: An intrauterine operation was the main reason for a thin EMT. Thin EMT patients with a normal uterine cavity and endometrium had a significantly better CLBR compared with those with adhesions before transfer.

The impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst.

BACKGROUND: The aim of this study was to explore the impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst. METHODS: This observational cohort study included a total of 3091 patients undergoing their first frozen-thawed embryo transfer (FET) cycles between April 2015 to March 2019. Endometrial thickness was measured by trans-vaginal ultrasound twice for each patient: on day of progesterone administration, and on day of embryo transfer. The change of endometrial thickness was recorded. RESULTS: Regardless of endometrial preparation protocol (estrogen-progesterone/natural cycle), female age, body mass index (BMI), and infertility diagnosis were comparable between patients with an increasing endometrium on day of embryo transfer and those without. However, clinical pregnancy rate increases with increasing ratio of endometrial thickness. Compared with patients with Non-increase endometrium, those with an increasing endometrium on day of embryo transfer resulted in significantly higher clinical pregnancy rate (56.21% vs 47.13%, P = 0.00 in estrogen-progesterone cycle; 55.15% vs 49.55%, P = 0.00 in natural cycle). CONCLUSIONS: In most patients, endometrial thickness on day of embryo transfer (after progesterone administration) increased or kept being stable compared with that on day of progesterone administration. An increased endometrium after progesterone administration was associated with better pregnancy outcome.

Analyses of optimal body mass index for infertile patients with either polycystic or non-polycystic ovary syndrome during assisted reproductive treatment in China.

We observed the effect of body mass index (BMI) on pregnancy outcomes in Chinese patients undergoing assisted reproductive treatment (ART). All the patients were divided into polycystic ovary syndrome (PCOS) group and non-PCOS group, and then according to BMI, each group was subdivided into 6 subgroups: group 1 (BMI < 18 kg/m2), group 2 (18-20 kg/m2), group 3 (20-22 kg/m2), group 4 (22-24 kg/m2), group 5 (24-26 kg/m2) and group 6 (BMI > 26.0 kg/m2). We found that in 20 to 25-year-old patients, the pregnancy rate was not significantly correlated with BMI in PCOS patients; while in non-POCS patients, the pregnancy rate significantly decreased at the BMI cut-off point value of 24-26 kg/m2. The pregnancy rate significantly declined at the BMI cut-off point values of 22-24 kg/m2 and 18-20 kg/m2, respectively in 25 to 35-year-old and in over 35-year-old PCOS patients; while in over 25-year-old non-PCOS patients, no significant correlation between pregnancy rate and BMI was observed. We conclude that for under 25-year-old non-PCOS patients, ART should be performed after BMI is controlled under 26 kg/m2. For PCOS patients, if age is 25 to 35 years or over 35 years, BMI should be controlled below 24 kg/m2 or below 20 kg/m2, respectively.

Growth hormone co-treatment within a GnRH agonist long protocol improves implantation and pregnancy rates in patients undergoing IVF-ET.

OBJECTIVE: The efficacy of growth hormone (GH) co-treatment within a GnRH agonist long regimen, in women with a normal ovarian response to controlled ovarian hyperstimulation (COH), for IVF was assessed. METHODS: This retrospective clinical trial was performed in a private-assisted reproduction centre. The study involved 1114 patients who responded normally to high-dose gonadotropin treatment. The study group of 556 patients was given in a daily subcutaneous injection of 4.5 IU of GH co-treatment, starting from the initial day of gonadotropin treatment and lasting for 5 days. The control group of 558 patients received the same treatment protocol without the GH co-treatment. The participants were further divided into two subgroups: age ≥35 years and age <35 years. The primary endpoint of the study was IVF-ET outcomes. RESULTS: The demographic characteristics did not significantly differ between the groups. The implantation rate (36.7 vs. 20.4 %, P < 0.05) and clinical pregnancy rate (57.3 vs. 30.1 %, P < 0.05) were significantly higher in the study group than in the control group. An analysis using a multivariate logistic regression model showed that GH was a significant factor for predicting pregnancy outcomes (OR 3.125, 95 % CI 2.441-4.000). Furthermore, for the ≥35-year-old group, the endometrial thickness was significantly greater (11.99 ± 2.21 vs. 11.62 ± 2.45, P < 0.05) in the study group than in the control group; in contrast, for the <35-year-old group, the high-quality embryo rate was significantly higher (71.7 vs. 68.3 %, P < 0.05) in the study group than in the control group. CONCLUSION: Our study showed that co-treatment with GH in a GnRH agonist long protocol in patients who responded normally while undergoing IVF-ET could increase the implantation and pregnancy rates.

[Effects of oral dydrogesterone on clinical outcomes of frozen-thawed embryo transfer cycles].

OBJECTIVE: To investigate the effects of oral dydrogesterone for luteal phase support after frozen embryo transfer (FET) cycles on the clinical outcomes. METHODS: A total of 1643 FET cycles in our center between January, 2010 and September, 2011 were analyzed. The patients were divided into group A with natural-cycle FET and group B with hormone replacement cycle (HRT-FET). The two groups were further divided into two subgroups to receive oral dydrogesterone (groups AI and BI, n=358 and 185, respectively) or intramuscular progesterone with progynova (groups AII and BII, n=634 and 466, respectively) as luteal phase support. The clinical pregnancy rates, implantation rates, early miscarriage rates, ectopic pregnancy rates, ongoing pregnancy rates and delivery rates were compared between the subgroups. RESULTS: There were no significant differences in the clinical outcomes between the patients receiving dydrogesterone and intramuscular progesterone as luteal phase support in either natural-cycle FET or HRT FET (P>0.05). CONCLUSION: In the FET cycles, oral dydrogesterone tablets for luteal support can achieve good clinical outcomes comparable with those by intramuscular progesterone and serves as a good alternative for luteal phase support.

Inhibitory effect of the paraoxonase gene on the formation of rabbit coronary atherosclerosis.

OBJECTIVE: To observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene (PON-1) which transfected to the rabbit epicardial adipose tissue. METHODS: Rabbit coronary atherosclerosis model was established by high-fat feeding, liposome-encapsulated recombinant plasmid pEGFP-PON-1 50 µ L was injected to the rabbit pericardial cavity, and was harvested 4 weeks after transfection. RESULTS: The epicardial fat transfected PON-1 gene had effect on the high lipid level. It significantly increased expression of PON-1 in peripheral arterial vascular tissue (P <0.05); and significantly reduced total cholesterol and low-density lipoprotein cholesterol levels (P<0.05), and the thickness ratio of coronary artery intima/media (P <0.05). CONCLUSIONS: The injection of the PON-1 gene in the pericardial cavity can effectively suppress the formation of coronary atherosclerosis.

Ovarian damage after laparoscopic endometrioma excision might be related to the size of cyst.

OBJECTIVE: To investigate the relationship between the size of an excised endometrioma and the magnitude of damage to the ovary after the surgery. DESIGN: A retrospective, controlled study. SETTING: A university hospital. PATIENT(S): Eighty-five women with a history of laparoscopic excision of unilateral endometrioma who underwent in vitro fertilization (IVF). INTERVENTION(S): IVF-embryo transfer procedures. MAIN OUTCOME MEASURE(S): Antral follicle counts (AFC), number of dominant follicles (follicles ≥ 15 mm), and number of oocytes retrieved. RESULT(S): In the group with cyst diameters of ≥ 4 cm and group with cyst diameters of <4 cm, the AFC, number of dominant follicles, and number of oocytes retrieved were decreased in the operated ovaries when compared with those in intact ovaries; in the former group, a statistically significant reduction was observed. The differences of AFC, number of dominant follicles, and number of oocytes retrieved from both ovaries were further compared among the two groups: the decrease in the group with cyst diameters of ≥ 4 cm was higher than in the group with cyst diameters of <4 cm. After adjusting for age and AFC in intact ovaries, similar results were obtained, although AFC only showed a tendency. In addition, the receiver operating characteristic curve analysis revealed a statistically significant, positive correlation between the size of excised cysts and the incidence of fewer than four oocytes retrieved from an operated ovary. CONCLUSION(S): The magnitude of the ovarian damage after laparoscopic endometrioma excision might be related to the size of cyst; the damage to ovaries is more severe when an endometrioma ≥ 4 cm is excised.

Circulating luteinizing hormone level after triggering oocyte maturation with GnRH agonist may predict oocyte yield in flexible GnRH antagonist protocol.

BACKGROUND: The use of gonadotrophin-releasing hormone (GnRH) agonist for triggering final oocyte maturation and ovulation can reduce ovarian hyperstimulation syndrome (OHSS) in high-risk patients. LH levels post-trigger with GnRH agonist might be correlated with oocyte yield and maturity. Our aim was to evaluate the relationship between serum LH level at 12-h post-trigger and oocyte yield, maturity and fertilization rate in patients at high risk of OHSS and therefore who were treated with a flexible GnRH antagonist protocol in which final oocyte maturation was triggered with GnRH agonist. METHODS: In a prospective cohort study, 91 patients at high risk of OHSS were treated with a flexible GnRH antagonist protocol and divided into six groups according to their serum LH levels at 12-h after GnRH agonist administration: ≤15.0, 15.1-30.0, 30.1-45.0, 45.1-60.0, 60.1-75.0 and >75.0 IU/l. The oocyte yield, maturity, fertilization rate and clinical outcomes for each LH interval were analyzed. RESULTS: There was a statistically significant reduction in oocyte yield with a concentration of serum LH ≤15.0 IU/l (P < 0.05), whereas no statistically significant differences in the oocyte maturity and fertilization rate among the six groups (P > 0.05) were seen. Only 5 out of 91 patients (5.5%) had a serum LH ≤15.0 IU/l at 12-h post-trigger with GnRH agonist. In addition, no statistically significant difference was seen regarding high-quality embryos, implantation rate, clinical pregnancy rate and early miscarriage between patients with LH ≤15.0 IU/l and >15.0 IU/l (P > 0.05). CONCLUSIONS: Serum LH level at 12-h post-trigger with GnRHa <15.0 IU/l is associated with a dramatically lower oocyte yield but not with the oocyte maturity and fertilization rate. Serum LH levels post-trigger with GnRH agonist do not affect clinical outcomes.

Low testosterone level in middle-aged male patients with coronary artery disease.

BACKGROUND: Endogenous testosterone has been shown to provide a protective role in the development of cardiovascular diseases in men. This study investigated the changes of testosterone level and its relationship to the severity of coronary artery stenosis in middle-aged men with coronary artery disease (CAD). METHODS: Serum testosterone concentration was measured in 87 middle-aged men patients with CAD including stable angina pectoris (SAP), unstable angina pectoris (USAP) and acute myocardial infarction (AMI). All patients underwent coronary angiography and the severity of coronary stenosis was estimated by the Gensini coronary score. The patients with the severity of coronary artery stenosis of less than 50% served as control group. RESULTS: The levels of testosterone in SAP group (488.2 ± 96.8ng/dl), USAP group (411.6 ± 128.6ng/dl) and AMI group (365.3 ± 116.6ng/dl) were significantly lower than that in control group (562.8 ± 110.2ng/dl) (all p<0.05). When compared with another group among SAP, USAP and AMI groups, the level of testosterone in the AMI group was the lowest, the USAP group was the median while the SAP group was the highest (all p<0.05). There was a significant correlation between angiographic Gensini score and testosterone level (n=87, r=-0.513, p<0.05). Multiple regression analysis found that testosterone and BMI were independent predictors for CAD (testosterone: odds ratio 0.311, 95% confidence interval 0.174-0.512; BMI: odds ratio 1.905, 95% confidence interval 1.116-2.973). CONCLUSION: The present study showed that middle-aged male patients with CAD present a lower level of serum testosterone and the testosterone level was negatively correlated with the severity of coronary artery stenosis.