Therapeutic effect of manual massage on early postpartum rectus abdominis separation and postpartum depression.

BACKGROUND: Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum depression. AIM: To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum women. METHODS: Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September 2023. The patients were divided into the Group S (35 cases, biomimetic electrical stimulation treatment) and Group L (35 cases, biomimetic electrical stimulation combined with manual massage treatment). Baseline data, the edinburgh postpartum depression scale (EPDS) score, and the visual analog scale (VAS) scores for rectus abdominis distance, waist circumference, and lower back pain before and after treatment were compared. RESULTS: No significant differences were found in the baseline data, rectus abdominis distance, waist circumference, and VAS and EPDS scores between the two groups before treatment (P > 0.05). After treatment, the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S (P < 0.05). Furthermore, lower back pain (VAS score) and the EPDS score in Group L were significantly lower than those in Group S (P < 0.05). CONCLUSION: Manual massage can significantly reduce early postpartum DRA, waist circumference, and back pain and improve the patient's mental state and postpartum depression.

A Meta-Analysis of Differences in Thyroid and Cardiac Function Between Women with Normal Pregnancies and Gestational Diabetes Mellitus.

Objective: This is a meta-analysis of thyroid function (TF) and cardiac function (CF) differences between women with normal pregnancies and gestational diabetes mellitus (GDM), in order to provide more reliable reference and guidance for the future clinical prevention and treatment of GDM. Methods: Studies on the correlation of GDM with TF and CF were searched in PubMed, Cochrane Library, and other literature databases, and the literature for final analysis was confirmed after screening according to the eligibility criteria. Authors, publication time, research subjects, and endpoints were extracted for meta-analysis using Review 5.3 software. Results: After screening, 10 studies with a total of 2554 subjects were selected, including 1125 GDM patients (GDM group) and 1429 normal pregnant women (control group). All the included papers scored 6-7 points on the Newcastle-Ottawa Scale used for literature quality evaluation, implying high-quality research. In the meta-analysis, the relationship between GDM and TF, TSH, and FT3 increased evidently in the GDM group, while FT4 decreased (P < .05). The meta-analysis of GDM and CF revealed lower LVEF and E/A while higher E/E' in GDM patients compared to the controls (P < .05). The funnel plot showed that the graphs of all the endpoints were basically symmetrical, indicating low publication bias. Conclusion: Given the obvious thyroid dysfunction and cardiac dysfunction in GDM patients, symptomatic intervention measures should be taken actively and timely to improve the safety of GDM patients during pregnancy.

Epitope-Directed Antibody Elicitation by Genetically Encoded Chemical Cross-Linking Reactivity in the Antigen.

No current methods can selectively elicit an antibody response to a specific conformational epitope in a whole antigen in vivo. Here, we incorporated Nε-acryloyl-l-lysine (AcrK) or Nε-crotonyl-l-lysine (Kcr) with cross-linking activities into the specific epitopes of antigens and immunized mice to generate antibodies that can covalently cross-link with the antigens. By taking advantage of antibody clonal selection and evolution in vivo, an orthogonal antibody-antigen cross-linking reaction can be generated. With this mechanism, we developed a new approach for facile elicitation of antibodies binding to specific epitopes of the antigen in vivo. Antibody responses were directed and enriched to the target epitopes on protein antigens or peptide-KLH conjugates after mouse immunization with the AcrK or Kcr-incorporated immunogens. The effect is so prominent that the majority of selected hits bind to the target epitope. Furthermore, the epitope-specific antibodies effectively block IL-1ß from activating its receptor, indicating its potential for the development of protein subunit vaccines.

Performance of human papillomavirus (HPV) mRNA testing and HPV 16 and 18/45 genotyping combined with age stratification in the triaging of women with ASC-US cytology.

OBJECTIVES: This study aimed to assess the clinical performance of an HPV E6/E7 mRNA assay (Aptima HPV, AHPV) and AHPV 16 18/45 genotype assay (AHPV-GT) combined with age stratification for triaging women with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: In total, 3052 women >21 years old with ASC-US cytology underwent AHPV testing, and AHPV-positive samples were reflex-tested with the AHPV-GT test. All women were referred for colposcopy and then biopsy if indicated. The AHPV and AHPV-GT test performances and risk estimates by hrHPV status with age stratification were calculated. RESULTS: Overall, 1599 women (52.4%) tested AHPV positive; of these women, 225 (7.4%), 101 (3.3%) and 1273 (41.7%) tested HPV 16+, HPV 18/45+ and other hrHPV-genotype-positive. When identifying CIN3+, the AHPV test had a 93.2% sensitivity and achieved a higher NPV (99.7% vs. 98.5%, P < 0.001) but a lower PPV (4.3% vs. 10.4%, P < 0.001) than the AHPV-GT test. The immediate risks of CIN3+ in AHPV+, other hrHPV+, and AHPV-GT+ women were 4.3%, 2.7%, and 10.4%, respectively. In the 21-24-year-old group, the immediate risks were 1.6%, 2.0% and 0.0%, which were below the 4.0% threshold for immediate colposcopy. The immediate colposcopy referral rate for AHPV-positive/ASC-US women 25 years or older was reduced from 51.7% to 10.5% by the AHPV-GT risk stratification method. CONCLUSIONS: AHPV testing with age stratification is effective for triaging women with ASC-US cytology. AHPV-GT testing may be a proper risk stratification method for women with AHPV-positive ASC-US cytology.

Coordinating antigen cytosolic delivery and danger signaling to program potent cross-priming by micelle-based nanovaccine.

Although re-activating cytotoxic T-cell (CTLs) response inside tumor tissues by checkpoint blockade has demonstrated great success in tumor immunotherapy, active induction of efficient endogenous CTL response by therapeutic vaccines has been largely hampered by inefficient cytosolic delivery of antigens and coordinated activation of dendritic cells (DCs) in lymph nodes. Here we show that polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles transform soluble peptides into α-helix to enable their efficient cytosolic delivery. The same PEG-PE micelles also serve as chaperon of TLR4 signaling to coordinate its adjuvant effect on the same DCs. Furthermore, these nanovaccines effectively target lymph node DCs. Thus, PEG-PE micelle vaccines program at multiple key aspects for inducing strong CTL responses and build up a foundation for combinational tumor therapy.

Associations of Promoter Methylations and mRNA Expressions of MMP-2, MMP-7 and MMP-9 with Primary Fallopian Tube Carcinoma.

OBJECTIVE: To explore the associations of matrix metalloprotease-2 (MMP-2), MMP-7 and MMP-9 methylations and messenger ribonucleic acid (mRNA) expressions with primary fallopian tube carcinoma (PFTC) development and prognosis. METHODS: We recruited 48 patients with PFTC into the case group and 48 healthy individuals into the control group; PFTC tissues and normal fallopian tube tissues were obtained from subjects in both groups. Methylation specific polymerase chain reaction (PCR), reverse transcription PCR and the immunohistochemical method were used to examine methylation, mRNA expressions and protein expressions of MMP-2, MMP-7 and MMP-9, respectively. RESULTS: The methylation rates of MMP-2, MMP-7 and MMP-9 in the case group were significantly lower than those in the control group (all p < 0.05); MMP-2, MMP-7 and MMP-9 protein and mRNA expressions of PFTC tissues were enormously higher than those of normal tissues (all p < 0.05); univariate survival analysis indicated that MMP-2 and MMP-9 methylations and their protein expressions were associated with PFTC prognosis (all p < 0.05), which was further confirmed by the Cox regression model (all p < 0.05). CONCLUSION: The protein and mRNA expressions of MMP-2, MMP-7 and MMP-9 might be related to PFTC, while the methylations and protein expressions of MMP-2 and MMP-9 might be associated with PFTC progression and prognosis.

Nano-cage-mediated refolding of insulin by PEG-PE micelle.

Insulin aggregation has pronounced pharmaceutical implications and biological importance. Deposition of insulin aggregates is associated with type II diabetes and instability of pharmaceutical formulations. We present in this study the renaturation effect of PEG-PE micelle on dithiothreitol (DTT)-denatured insulin revealed by techniques including turbidity assay, circular dichroism (CD), thioflavinT (ThT) binding assay, bis-ANS binding assay, agarose gel electrophoresis and MALDI-TOF MS. The obtained results show that PEG-PE micelle having a hydrophilic nano-cage-like structure in which with a negative charge layer, can capture DTT-induced insulin A and B chains, and block their hydrophobic interaction, thereby preventing aggregation. The reduced insulin A and B chain in the nano-cage are capable of recognizing each other and form the native insulin with yields of ∼30% as measured by hypoglycemic activity analysis in mice. The observed insulin refolding assisted by PEG-PE micelle may be applicable to other proteins.

Lysosome-oriented, dual-stage pH-responsive polymeric micelles for ß-Lapachone delivery.

ß-Lapachone (ß-lap), a novel anticancer agent, is bioactivated by NADP(H):quinone oxidoreductase 1 (NQO1), an enzyme over-expressed in numerous tumors, including lung, pancreas, breast, and prostate cancers. Fast renal clearance and methemaglobinemia / hemolytic side-effects from the clinical formulation (ß-lap-hydroxyl propyl-ß-cyclodextrin complex) hindered its clinical translation. Here, we investigated a dual model pH responsive polymers for ß-lap delivery. Three pH-sensitive linkages, including acylhydrazone, ketal and imine bonds for ß-lap prodrug syntheses result in an aryl imine linkage the most optimal linkage. The conversion to ß-lap was 2.8%, 4.5% and 100% at pH 7.4, 6.5 and 5.0 in 8 h, respectively. ß-lap aryl imine prodrug conjugated ultra pH-sensitive (UPS) polymer reached high ß-lap loading density (8.3%) and exhibited dual-stages responsiveness to pH variation. In pHs under pHt, at stage I, micelle immediately dissociation and subsequently entering stage II, micelles start quickly release ß-lap. In vitro release study showed that the micelles constantly release ß-lap (14.9 ± 0.1%) at pHs above pHt in 72 h, whereas boosted release of ß-lap (79.4 ± 1.2%) at pH 5.0. Micelle intracellular distribution predominantly in the lysosome organelle guaranteed their pH responsive dissociation and subsequently ß-lap controlled release. The M-P micelles retained NQO1-dependent cytotoxicity in A549 lung cancer cells, similar to free drug in both efficacy and mechanism of cell death. The lysosome-oriented dual-stage ultra pH responsive ß-lap prodrug micelles potentially offer an alternative nanotherapeutic strategy for lung, as well as other NQO1+ cancer therapies.

Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.

RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early.

A class of novel Schiff's bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis.

To discover analgesics for treating chronic pain 17 novel Schiff's bases, N,N'-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 micromol/kg of these Schiff's bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 micromol/kg of these Schiff's bases exhibited desirable anti-inflammation. Thus the present Schiff's bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff's bases on the analgesic activity was explained with 3D QSAR.