Objective:To compare the clinical outcomes of single oral dydrogesterone with vaginal progesterone gel plus oral dydrogesterone in gonadotropin-releasing hormone (GnRH) antagonist cycles with fresh embryo transfer.Methods:This study retrospectively analyzed 658 treatment cycles of fresh embryo transfer cycle with GnRH antagonist protocol from December 2015 to December 2020 in the Center of Reproductive Medicine of the University of Hong Kong-Shenzhen Hospital. Each cycle was the first fresh stimulation cycle of the patients. The patients were divided into two groups according to different luteal support regimens. Group A included 368 cycles with a regimen of 30 mg dydrogesterone tablets orally daily, while group B included 290 cycles with a regimen of 90 mg vaginal progesterone gel vaginally daily combined with 20 mg dydrogesterone tablets orally daily. A 1∶1 propensity score matching (PSM) was carried out to adjust for numerical differences and to balance between the two groups, and further they were divided into cleavage stage embryo transfer cycles and the blastocyst transfer cycles according to the different type of embryo for layer analysis, and the laboratory results and assisted reproductive outcomes of the two groups were compared.Results:After matching, the baseline characteristics were comparable between the two groups, with 251 cycles remaining in each group for retrospective analysis. After PSM, statistically significant differences were observed between group A and group B in laboratory data including the number of fertilized oocytes [5 (2, 7) vs. 6 (3, 9), P=0.002], cleavage rate [100.0% (86.31%, 100.0%) vs. 87.28% (75.32%, 100.0%), P<0.001], and available embryo rate [80.18% (54.64%, 100.0%) vs. 67.48% (50.62%, 100.0%), P=0.019]. However, there were no significantly statistical differences in other laboratory data and clinical outcomes (all P>0.05). If we divided the data into two comparison according to the different type of embryo, there were no significantly statistical differences in clinical pregnancy rate, embryo implantation rate, live birth rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation syndrome incidence, and ectopic pregnancy rate neither in day 2 cleavage stage embryo transfer cycles nor in the blastocyst transfer cycles. Conclusion:In this study, the clinical outcomes are similar between taking 30 mg of dydrogesterone tablets orally alone and taking 20 mg of dydrogesterone tablets orally combined with vaginal progesterone gel in the fresh embryo transfer cycle of the GnRH antagonist protocol. Moreover, taking dydrogesterone tablets orally alone can be a new option for luteal support in the fresh cycle of the GnRH antagonist protocol.

Objective:To compare the clinical outcomes of single oral dydrogesterone with vaginal progesterone gel plus oral dydrogesterone in gonadotropin-releasing hormone (GnRH) antagonist cycles with fresh embryo transfer.Methods:This study retrospectively analyzed 658 treatment cycles of fresh embryo transfer cycle with GnRH antagonist protocol from December 2015 to December 2020 in the Center of Reproductive Medicine of the University of Hong Kong-Shenzhen Hospital. Each cycle was the first fresh stimulation cycle of the patients. The patients were divided into two groups according to different luteal support regimens. Group A included 368 cycles with a regimen of 30 mg dydrogesterone tablets orally daily, while group B included 290 cycles with a regimen of 90 mg vaginal progesterone gel vaginally daily combined with 20 mg dydrogesterone tablets orally daily. A 1∶1 propensity score matching (PSM) was carried out to adjust for numerical differences and to balance between the two groups, and further they were divided into cleavage stage embryo transfer cycles and the blastocyst transfer cycles according to the different type of embryo for layer analysis, and the laboratory results and assisted reproductive outcomes of the two groups were compared.Results:After matching, the baseline characteristics were comparable between the two groups, with 251 cycles remaining in each group for retrospective analysis. After PSM, statistically significant differences were observed between group A and group B in laboratory data including the number of fertilized oocytes [5 (2, 7) vs. 6 (3, 9), P=0.002], cleavage rate [100.0% (86.31%, 100.0%) vs. 87.28% (75.32%, 100.0%), P<0.001], and available embryo rate [80.18% (54.64%, 100.0%) vs. 67.48% (50.62%, 100.0%), P=0.019]. However, there were no significantly statistical differences in other laboratory data and clinical outcomes (all P>0.05). If we divided the data into two comparison according to the different type of embryo, there were no significantly statistical differences in clinical pregnancy rate, embryo implantation rate, live birth rate, miscarriage rate, multiple pregnancy rate, ovarian hyperstimulation syndrome incidence, and ectopic pregnancy rate neither in day 2 cleavage stage embryo transfer cycles nor in the blastocyst transfer cycles. Conclusion:In this study, the clinical outcomes are similar between taking 30 mg of dydrogesterone tablets orally alone and taking 20 mg of dydrogesterone tablets orally combined with vaginal progesterone gel in the fresh embryo transfer cycle of the GnRH antagonist protocol. Moreover, taking dydrogesterone tablets orally alone can be a new option for luteal support in the fresh cycle of the GnRH antagonist protocol.

The interventional therapy of vascular stent implantation is a popular treatment method for cardiovascular stenosis and blockage. However, traditional stent manufacturing methods such as laser cutting are complex and cannot easily manufacture complex structures such as bifurcated stents, while three-dimensional (3D) printing technology provides a new method for manufacturing stents with complex structure and personalized designs. In this paper, a cardiovascular stent was designed, and printed using selective laser melting technology and 316L stainless steel powder of 0-10 µm size. Electrolytic polishing was performed to improve the surface quality of the printed vascular stent, and the expansion behavior of the polished stent was assessed by balloon inflation. The results showed that the newly designed cardiovascular stent could be manufactured by 3D printing technology. Electrolytic polishing removed the attached powder and reduced the surface roughness Ra from 1.36 µm to 0.82 µm. The axial shortening rate of the polished bracket was 4.23% when the outside diameter was expanded from 2.42 mm to 3.63 mm under the pressure of the balloon, and the radial rebound rate was 2.48% after unloading. The radial force of polished stent was 8.32 N. The 3D printed vascular stent can remove the surface powder through electrolytic polishing to improve the surface quality, and show good dilatation performance and radial support performance, which provides a reference for the practical application of 3D printed vascular stent.
Humans ; Stainless Steel ; Powders ; Cardiovascular System ; Constriction, Pathologic

Objective To investigate the levels of γδ T cells and their subpopulations in bone marrow(BM)of patients with myelodysplastic syndrome(MDS),it aims to explore the immune deficiency status of BM microenvi-ronment in MDS patients.Methods BM samples were collected from MDS patients before and after treatment,as well as from normal donors.Multicolor flow cytometry was utilized to detect bone marrow γδ T cells and subpopulation levels.The changes of the T cell subsets after treatment were also analyzed.Results The levels of BM γδ T cells and follicular helper γδ T cells from MDS patients were significantly lower than those of normal donors(P<0.05).Among γδ T cells at different stages of differentiation,only the frequencies of na?ve γδ T cells from MDS patients decreased significantly(P = 0.037),and there was no significant difference observed about central memory,effector memory,and terminally differentiated γδ T cells in MDS patients compared to normal donors(P>0.05).Although there was a slight decrease in PD1+γδ T cells and an increase in TIM3+γδ T cells,these differences were not statistically significant(P>0.05).In patients who achieved a curative effect,the proportions of γδ T cells and naive γδ T cells increased significantly after treatment,and the effector memory γδ T cells decreased significantly after treatment(P<0.05).After treatment,85.71%(6/7)of MDS patients showed a decrease in γδ+TIM3+ T cell levels to varying degrees.Conclusions The levels of γδ T cells and their subpopulations in the BM microenvironment of patients with MDS exhibit varying degrees of abnormalities.However,in patients who receive effective treatment,these abnormal γδ T cells can recover.By detecting the levels of γδ T cells and subpopulations,we can gain insights into the immune deficiency status of MDS.This information might serve as an indicator to assess treatment efficacy and provide valuable insights for anti-tumor immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective:To explore the risk factors of bacterial infections in patients with decompensated hepatitis B cirrhosis and to construct a risk prediction model.Methods:The clinical data of 198 patients with decompensated hepatitis B cirrhosis admitted in Zhejiang Provincial People’s Hospital from January 2014 to April 2020 were retrospectively analyzed. There were 86 patients with bacterial infection (infection group) and 112 patients without bacterial infections (non-infection group). The risk factors of bacterial infections were analyzed by multivariate Logistic regression. R language was used to establish a nomogram model to predict the risk of bacterial infection in patients with decompensated hepatitis B cirrhosis. Receiver operating characteristic (ROC) curve was used to explore the prediction efficiency of the nomogram model for bacterial infection.Results:Multivariate logistic regression analysis showed that previous smoking history, prothrombin time, neutrophil count and hypersensitive C protein were independent risk factors for bacterial infection in patients with decompensated hepatitis B cirrhosis ( P<0.05 or <0.01), while regular antiviral treatment and high-density lipoprotein were protective factors ( P<0.05 or <0.01). ROC curve showed that the area under the curve (AUC) of risk prediction model for bacterial infections was 0.872 (95% CI 0.820-0.924, P<0.01), and AUC of MELD score for predicting bacterial infections was 0.670 (95% CI 0.599-0.735, P<0.01); the risk prediction model was superior to MELD score in prediction ( Z=4.89, P<0.01). Conclusions:The established risk prediction model in this study can more accurately predict the occurrence of bacterial infections in patients with decompensated hepatitis B cirrhosis.

Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10⁶ bone marrow cells with 8×10⁶ spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4⁺ T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ²=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.

Objective: To monitor the WT1 mRNA level and its dynamic changes in patients with myelodysplastic syndromes (MDS) after hypomethylating agents (HMA) , as well as to assess the significance of WT1 mRNA levels and its dynamic changes in evaluating the efficacy of HMA and distinguishing the disease status of heterogeneous patients with stable disease (SD) . Methods: Bone marrow or peripheral blood samples of 56 patients with MDS who underwent hypomethylating agents (≥4 cycles) from November 2009 to March 2018 were tested by real-time quantitative polymerase chain reaction (PCR) to detect the expression of WT1 mRNA, and to observe the correlation between the dynamic changes of WT1 mRNA expression and clinical efficacy and prognosis of patients. Results: WT1 mRNA expression levels of MDS patients decreased significantly after 3 cycles of hypomethylating agent treatment. Besides, the WT1 mRNA expression levels of patients increased significantly after diseases progression. According to the dynamic changes of WT1 mRNA expression levels during SD, 45 cases could be further divided into increased group and non-increased group. In those SD patients with increased WT1 mRNA expression level, the ratio of suffering disease progression or transformation to AML was 95.65% (22/23) , whereas the ratio turned to be 9.09% (2/22) for the non-increased group (χ²=33.852, P<0.001) . Compared with those SD patients reporting no increase in WT1 mRNA expression level, the overall survival[17 (95%CI 11-23) months vs not reached, P<0.001] and progression-free survival [13 (95%CI 8-18) months vs not reached, P<0.001] of those SD patients reporting increase in WT1 mRNA expression level were significantly shorter. Conclusion WT1 mRNA expression level is a useful indicator to assess the efficacy of hypomethylating agents in MDS patients. Especially in patients with SD, detection of the changes in WT1 mRNA expression level is able to predict disease progression and help to make clinical decision.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine