Which vaginal douching agent is the best choice before oocyte retrieval? A systematic review and network meta-analysis.

Objective: The aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium permanganate) on oocytes pick-up related pelvic infection (OPU-PI) and IVF outcome in patients underwent assisted reproduction technology (ART). Design: Through searching PubMed, Embase, Cochrane Library, Web of Science, Ovid, CINAHL CNKI, only human clinical trials were collected to study the effects of the six vaginal douching agents on OPU-PI and IVF outcomes. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. Results: The clinical trials were collected between the earliest available date and June 2022. Eight studies were included, the total sample size used in the study was 12,567. The results of the network meta-analysis showed that Ozone can significantly decrease OPU-PI; Iodine followed by saline can be a antiseptic protocol ranked first without affecting the quality of oocytes and Chlorhexidine acetate followed by saline can improve patients' clinical pregnancy rate. Conclusion: Based on Ranking Plot of the Network, this review reports the best evidence available regarding different vaginal douching agents used before OPU.

Hydrophobic interaction chromatography (HIC) method development and characterization of resolved drug-load variants in site-specifically conjugated pyrrolobenzodiazepine dimer-based antibody drug conjugates (PBD-ADCs).

Antibody drug conjugates (ADCs) are heterogeneous biopharmaceutical products that demand extensive characterization to ensure batch consistency, safety, and efficacy. Hydrophobic interaction chromatography (HIC) is the state-of-the-art analytical tool to monitor conjugation-related critical quality attributes (CQAs) e.g. drug-load distribution and Drug-to-Antibody Ratio (DAR). For the next generation site-specific PBD-ADCs (PBD: pyrrolobenzodiazepine dimer), denaturing RP-HPLC (reverse-phase high-performance chromatography) is the current method to determine average DAR. In this manuscript, we have utilized native HIC for the first time to understand conjugation related CQAs in PBD-ADCs. In terms of the method development, the type of stationary phase and salt, coupled with reduction of the reactive imine in the PBD drug-linker to an amine form in the sample preparation, have played a key role in achieving the best HIC resolution for the drug-load variants. The established HIC conditions resolved DAR 0, DAR 1, and two DAR 2 peaks for PBD-ADCs. Extended characterization of the DAR 2 peaks confirmed that they have retained characteristically distinct antibody Fc N-glycan distributions (Fc = Fragment crystallization region). Therefore, the results support that the HIC conditions established for PBD-ADCs is valuable in not only determining DAR values but also other important attributes including native drug-load distribution and unique DAR 2 conformations existed as a result of the N-glycan heterogeneity.

Proteomic analysis of meningiomas.

Meningiomas represent one-third of all primary brain tumors and cause 35,000 new cases each year. Because of this high incidence, we sought to determine if there are proteomic differences between meningiomas and neighboring tissues. Two-dimensional gel electrophoresis and mass spectrometry were used to detect differentially expressed proteins in tumor samples, using arachnoid tissue as a control. Western blot analysis was used to validate the identified candidate proteins. We obtained quantitative data on 112 proteins, 17 of which were down-regulated and 26 of which were up-regulated in meningiomas relative to normal arachnoid tissue. Our analysis showed that the expression of galectin-3, vimentin, and endoplasmin was decreased significantly in meningiomas. The expression of 40S ribosomal protein S12, glutathione S-transferase P, and hypoxia up-regulated protein 1 was increased significantly (P < 0.05). The six above-mentioned differentially expressed proteins might be closely involved with the development of meningiomas. The results of this study provide basic insights into the proteome of meningiomas and provide a preliminary database for further research to enhance understanding of meningioma development.

Water-soluble prodrugs of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir.

We studied the synthesis, cleavage rates, and oral administration of prodrugs of the HIV protease inhibitors (PIs) lopinavir and ritonavir. Phosphate esters attached directly to the central hydroxyl groups of these PIs did not demonstrate enzyme-mediated cleavage in vitro and did not provide measurable plasma levels of the parent drugs in vivo. However, oxymethylphosphate (OMP) and oxyethylphosphate (OEP) prodrugs provided improved rates of cleavage, high levels of aqueous solubility, and high plasma levels of the parent drugs when dosed orally in rats and dogs. Dosing unformulated capsules containing the solid prodrugs led to plasma levels equivalent to those observed for dosing formulated solutions of the parent drugs. A direct synthetic process for the preparation of OMP and OEP prodrugs was developed, and the improved synthetic method may be applicable to the preparation of analogous soluble prodrugs of other drug classes with limited solubility.

Expression of insulin-like growth factor II and its receptor in liver cells from patients with chronic liver diseases.

AIM: To study the relationship between insulin-like growth factor II (IGF-II), IGF-II receptor, and chronic liver diseases and to investigate the clinical mechanisms of human hepatocellular carcinoma (HCC) development. METHODS: We analyzed IGF-II and IGF-II receptor poly (A)+ mRNA in dysplasia liver cell (DLC; n = 10), liver cirrhosis (LC; n = 9), and chronic active hepatitis (CAH; n = 9) specimens by Northern blot using human IGF-II and IGF-II receptor DNA probes labeled with (32) P through nick translation. RESULTS: Expression of IGF-II in DLC samples (10/10, 100%) was higher than in CAH (3/9, 33%) and LC samples (3/9, 33%) (P < 0.01). Expression of IGF-II receptor in DLC samples (7/10, 70%) was significantly higher than in CAH (2/9, 22%) and LC samples (3/9, 33%). Data on hepatitis B virus (HBV) infection status from different chronic liver disease samples were also analyzed. CONCLUSION: Overexpression of IGF-II and IGF-II receptor in DLC samples was associated with a preceding step to malignant phenotype hepatocyte transformation and may be of diagnostic value for early detection of hepatocellular carcinoma (HCC). Persistent HBV infection was strongly associated with abnormal IGF-II and IGF-II receptor mRNA expression, suggesting that an autocrine or paracrine mechanism is involved in the regulation of growth in liver cell carcinogenesis.