Computational screening of metalloporphyrin-based drug carriers for antitumor drug 5-fluorouracil.

Developing novel nanoscale carriers for drug delivery is of great significance for improving treatment efficiency and reducing side effects of antitumor drugs. In view of the good biocompatibility and special affinity of porphyrin (PP) molecule to cancer cells, it was used to construct a series of metal-doped M@PP (M = Ca âˆ¼ Zn) materials for the delivery of anticancer drug 5-fluorouracil (5-Fu) in this work. Our results reveal that 5-Fu is tightly adsorbed on M@PP (M = Ca âˆ¼ V, Mn âˆ¼ Co, and Zn) by chemisorption, but is physically adsorbed by M@PP (M = Cr, Ni, and Cu). The calculated electronic properties show that all these 5-Fu@[M@PP] (M = Ca âˆ¼ Zn) complexes have both high stability and solubility. Among these 5-Fu@[M@PP] complexes, the chemical bond formed between 5-Fu and Ti@PP has the strongest covalent characteristic, resulting in the largest adsorption energy of -19.93 kcal/mol for 5-Fu@[Ti@PP]. In particular, 5-Fu@[Ti@PP] has the proper recovery time under the near-infrared light at body temperature, which further suggests that Ti@PP is the best drug carrier for 5-Fu. This study not only reveals the interaction strength and nature between 5-Fu and M@PP, but also confirmed the intriguing potential of Ti@PP as nano-carrier for drug delivery. However, further experimental research should be conducted to verify the conclusion obtained in this work.

Obstetric and perinatal outcomes following frozen and fresh embryo transfer in patients with endometrial hyperplasia and carcinoma: a retrospective study in a high-volume reproductive center.

BACKGROUND: There is ongoing debate regarding which embryo transfer procedure can achieve a higher live birth rate. Research has suggested that frozen ET might be beneficial for certain populations, such as hyper-responders. This study aimed to compare outcomes of pregnancies between frozen and fresh embryo transfer cycles in patients with endometrial hyperplasia and carcinoma. METHODS: This retrospective cohort study was conducted at a high-volume reproductive center from January 2010 to January 2022. Patients who were diagnosed with endometrial hyperplasia with atypia and endometrial carcinoma were included. They all underwent in vitro fertilization after conservative treatment. The primary outcome was live birth after frozen and fresh embryo transfer cycles, and secondary outcomes included perinatal complications and other pregnancy outcomes. RESULTS: Overall, 259 ET cycles (130 fresh and 129 frozen) were included. The rate of live births per embryo transfer cycle of the whole cohort was 20.8% (54/259), and no significant between-group difference was found after adjusting for potential confounding factors (23.8% vs. 17.8%; adjusted OR, 0.47; 95% CI, 0.21-1.06; p=0.068). Compared to fresh embryo transfer group, the incidence of total maternal complications in the frozen embryo transfer group was significantly higher (30.4% vs. 6.5%, p=0.019). Analyzing each complication as a separate entity, patients in the frozen embryo transfer group had a higher incidence of hypertensive disorders of pregnancy (p=0.028). Multiple logistic regression analysis showed that frozen embryo transfer was related with an increased occurrence of maternal complications (OR, 6.68, 95% CI, 1.01-44.19, p=0.040). CONCLUSIONS: Among patients with endometrial hyperplasia and carcinoma, the rate of live births was comparable between both embryo transfer procedures, while frozen embryo transfer might be associated with a higher risk of maternal complications compared to that with fresh embryo transfer.

Analysis of Factors Associated With Recurrence of Early-Stage Endometrial Carcinoma and Atypical Endometrial Hyperplasia in Infertile Women After In Vitro Fertilization Treatment.

Purpose: To explore the relationship between different artificial reproductive treatment (ART) strategies and tumor outcomes, by analyzing clinical data of patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH). Methods: This retrospective study was performed in a tertiary hospital. Patients (n=131) with EC or AEH, who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment between June 2010 and June 2021, were divided into a recurrence group and a non-recurrence group. Clinical characteristics and tumor outcomes were assessed. Results: 131 patients were followed up for 4-132 months; 33 patients had recurrence, the recurrence rate was 25.2%, 3-year recurrence-free survival (RFS) rate was 83.2 ± 3.4%, and the 5-year RFS rate was 72.9 ± 4.4%. Factors including the frequency of controlled ovarian stimulation (COS) and the total days of ovarian stimulation had no significant effect on the recurrence of tumor lesions (p=0.368 and 0.969, respectively). Histology type (HR: 4.94, 95%CI: 2.41-10.15, p <0.001) and successful/un successful live birth (HR: 0.30, 95%CI: 0.14-0.65, p=0.003) were independent factors of recurrence. Twenty-two of the 82 patients who received a single COS had recurrence. Different COS protocols, the total dose of gonadotropin (Gn), and the serum E2 level on the trigger day had no significant effect on recurrence (p=0.326, 0.889 and 0.468, respectively). Conclusions: The degree at which an endometrial lesion progresses into carcinoma is a key factor affecting the recurrence of EC/AEH in patients after IVF/ICSI treatment, and successful live birth is a protective factor for the recurrence of endometrial lesions. Different COS protocols and COS frequencies, as well as the dosage and duration of Gn used during IVF did not affect the recurrence of endometrial lesions.

Analysis of IVF/ICSI outcomes in infertile women with early-stage endometrial cancer and atypical endometrial hyperplasia after conservative treatment.

PURPOSE: To investigate the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and identify factors that might affect live births in patients with early-stage endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH). METHODS: This retrospective study was performed in a tertiary hospital. Patients (n = 123) with EEC or AEH, who underwent IVF/ICSI treatment between January 2010 and December 2019, were divided into a live birth group and a non-live birth group. Clinical characteristics and IVF/ICSI outcomes were assessed. RESULTS: A total of 123 patients (28 with EEC and 95 with AEH) underwent 215 ovarian stimulation cycles, resulting in 121 fresh embryo transfer (ET) and 108 frozen-thawed ET. Among 229 ET cycles, 91 (23.7%) of 384 embryos were implanted and 86 pregnancies were achieved, including five ectopic pregnancies (5.8%), 28 miscarriages (32.6%), and 53 live births (61.6%). The clinical pregnancy and live birth rates in each ET cycle were 37.6% and 23.1%, respectively. Fifty-one patients gave birth to 57 live neonates, and the cumulative live birth rate was 41.46%. Multiple logistic regression analysis showed that maternal age, histological type, thin endometrium, and time after complete remission (CR) to IVF cycle started were significantly associated with live births. CONCLUSIONS: The live birth rate after IVF/ICSI is promising in infertile patients with EEC and AEH. A shorter interval between CR and IVF/ICSI treatment might be a positive factor, while age > 35 years, endometrial thickness < 8 mm on the day of ET, and degree of endometrial lesion progressing into carcinoma can negatively influence IVF/ICSI outcomes.

Amino-functionalized hypercrosslinked polymer as sorbent for effective extraction of nitroimidazoles from water, drink and honey samples.

The three hypercrosslinked polymers (HCP) materials, designated as OPD-HCP, MPD-HCP and PPD-HCP, were synthesized by using o-phenylenediamine (OPD), m-phenylenediamine (MPD) and p-phenylenediamine (PPD) as monomers. They were characterized by infrared spectroscopy, powder X-ray diffraction, nitrogen sorption isotherms, and scanning electron microscopy. Then, the HCPs were explored as solid-phase extraction (SPE) adsorbent for the extraction of five nitroimidazoles (NDZs) (metronidazole, ronidazole, secnidazole, dimetridazole and ornidazole). Among the three HCPs, the MPD-HCP has the best adsorption performance for the NDZs. With the help of high-performance liquid chromatography with ultraviolet detection (HPLC-UV), good linear response range (0.07-40.0 ng mL-1), high method recovery (86.8%-113.3%), low limits of detection (0.02-0.15 ng mL-1) and good precision with the relative standard deviations of less than 8.1% were achieved for the determination of the NDZs in water samples. The effective determination of the NDZs in peach juice, honey tea, and honey samples were also realized by the developed method with satisfactory results. Based on both the experimental results and density functional theory calculation, the adsorption mechanism can be attributed to multiple interactions between the MPD-HCP and the NDZs, including hydrogen bonding, hydrophilic, and electrostatic interactions. The method provides a new alternative of choice for the determination of some NDZs in real samples.

Low expression of NCOA5 predicts poor prognosis in human cervical cancer and promotes proliferation, migration, and invasion of cervical cancer cell lines by regulating notch3 signaling pathway.

Nuclear receptor coactivator 5 (NCOA5) specifically enhances estrogen receptor α-modulated transcriptional activity. As a novel tumor suppressor, depletion of NCOA5 is associated with the development of a variety of tumors, but its function in cervical cancer is currently unclear. In this study, we addressed how expression of NCOA5 changed in the development of human cervical cancer and its association with clinicopathological features, prognosis, and biology characteristics of cervical cancer. Analysis of the microarrays in the Oncomine database indicated that NCOA5 expression was lower in human cervical squamous cell carcinoma tissues than that in normal cervical tissues. That was corroborated by our experiments using fresh tissues: the expression levels of NCOA5 messenger RNA and protein were both significantly decreased in cervical cancer tissues compared with paired adjacent nontumor tissues (P < 0.01). Low expression of NCOA5 is associated with the International Federation of Gynecology and Obstetrics stage ( P = 0.043) and histological grade ( P = 0.018) of human cervical cancer. In addition, patients possessing low NCOA5 expression had poorer prognosis. Univariate and multivariate Cox regression analyses indicated that low NCOA5 expression may be an independent prognostic factor for poorer overall survival in cervical cancer. Further, downregulation of NCOA5 expression results in a significant increase in proliferation, migration, and invasion of HeLa cells. Data of xenograft tumor on BALB/c nude mice manifested that HeLa cells with low NCOA5 expression tend to form larger tumors than negative control ones. In contrast, overexpression of NCOA5 expression leads to the opposite results. Finally, we found that NCOA5 might affect the biological function of human cervical cancer cells by mediating the notch3 signaling pathway. These findings suggest that NCOA5 acts as a tumor suppressor to inhibit tumorigenicity, migration, and invasion, and thus represents a potential novel prognostic marker for overall survival in cervical cancer.