Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer.

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.

JAK2-Mediated Phosphorylation of Stress-Induced Phosphoprotein-1 (STIP1) in Human Cells.

Stress-induced phosphoprotein-1 (STIP1)-a heat shock protein (HSP)70/HSP90 adaptor protein-is commonly overexpressed in malignant cells, where it controls proliferation via multiple signaling pathways, including JAK2/STAT3. We have previously shown that STIP1 stabilizes the protein tyrosine kinase JAK2 in cancer cells via HSP90 binding. In this study, we demonstrate that STIP1 may act as a substrate for JAK2 and that phosphorylation of tyrosine residues 134 and 152 promoted STIP1 protein stability, induced its nuclear-cytoplasmic shuttling, and promoted its secretion into the extracellular space. We also found that JAK2-mediated STIP1 phosphorylation enhanced cell viability and increased resistance to cisplatin-induced cell death. Conversely, interference STIP1 with JAK2 interaction-attained either through site-directed mutagenesis or the use of cell-penetrating peptides-decreased JAK2 protein levels, ultimately leading to cell death. On analyzing human ovarian cancer specimens, JAK2 and STIP1 expression levels were found to be positively correlated with each other. Collectively, these results indicate that JAK2-mediated phosphorylation of STIP-1 is critical for sustaining the JAK2/STAT3 signaling pathway in cancer cells.

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.

Designing for effective controlled release in agricultural products: new insights into the complex nature of the polymer-active agent relationship and implications for use.

BACKGROUND: Various active chemical agents, such as soil microbial inhibitors, are commonly applied to agricultural landscapes to optimize plant yields or minimize unwanted chemical transformations. Dicyandiamide (DCD) is a common nitrification inhibitor. However, it rapidly decomposes under warm and wet conditions, losing effectiveness in the process. Blending DCD with an encapsulating polymer matrix could help overcome this challenge and slow its release. Here, we encapsulated DCD in a biodegradable matrix of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and investigated the effects of DCD crystal size and loading rates on release rates. RESULTS: Three DCD crystal size fractions (0-106, 106-250 and 250-420 µm) were blended with PHBV at 200, 400, 600 and 800 gkg-1 loadings through extrusion processing and release kinetics were studied in water over 8 weeks. For loadings ≥ 600 g kg-1 , more than 95% release was reached within the first 7 days. By contrast, at 200 g kg-1 loading only 10%, 36% and 57% of the DCD was mobilized after 8 weeks in water for 0 to 106 µm, 106 to 250 µm and 250 to 420 µm crystal size fractions, respectively. CONCLUSION: The lower percolation threshold for this combination of materials lies between 200 and 400 g kg-1 DCD loading. The grind size fraction of DCD significantly affects the quantity of burst release from the surface of the pellet, particularly below the lower percolation threshold. The results presented here are likely translatable to the encapsulation and release of other crystalline materials from hydrophobic polymer matrices used in controlled release formulations, such as fertilizers, herbicides and pesticides. © 2020 Society of Chemical Industry.

The aggregation of casein micelles induced by Ca2+ during in vitro digestion: effects on the release of loaded anthocyanins.

Colloidal calcium phosphate (CCP) confers a modifiable structure to micellar casein (MC), which endows it with potential advantages as a delivery carrier. However, it is difficult to achieve multipattern release of the core material in the intestine with MC as a single wall. In this study, we prepared an anthocyanin-casein-based delivery system utilizing MC with different freezing degrees as the wall material with the objective of achieving the controlled release of anthocyanin as the model core in the intestine. The results showed that freezing could significantly reduce the CCP level up to 50%. Static in vitro simulated digestion with the addition of exogenous Ca2+ showed that the designed delivery system exhibited low anthocyanin release (15%-35%) in the gastric tract. The pattern of release in the intestine depended on the CCP dissociation degree. High and low dissociation degrees corresponded to slow release (from 15% to 65% within 2 h) and burst release (from 35% to 90% within 5 min), respectively. WAXS/SAXS analysis revealed that exogenous serum Ca2+ inherent in simulated gastric fluid and endogenous serum Ca2+ induced by CCP dissociation was synergistically involved in the reconstitution of CCP-mediated nanoclusters and large aggregates. The freezing degree of MC determined the endogenous serum Ca2+ level, which influenced the gastric aggregation behavior of wall MC and ultimately led to a fairly different gastrointestinal release behavior of anthocyanins.

Effects of Chlorogenic Acid on Lowering IgE-Binding Capacity of Soybean 7S: Comparison between Covalent and Noncovalent Interaction.

Allergenicity of soybean 7S protein (7S) troubles many people around the world. However, many processing methods for lowering allergenicity is invalid. Interaction of 7S with phenolic acids, such as chlorogenic acid (CHA), to structurally modify 7S may lower the allergenicity. Hence, the effects of covalent (C-I, periodate oxidation method) and noncovalent interactions (NC-I) of 7S with CHA in different concentrations (0.3, 0.5, and 1.0 mM) on lowering 7S allergenicity were investigated in this study. The results demonstrated that C-I led to higher binding efficiency (C-0.3:28.51 ± 2.13%) than NC-I (N-0.3:22.66 ± 1.75%). The C-I decreased the α-helix content (C-1:21.06%), while the NC-I increased the random coil content (N-1:24.39%). The covalent 7S-CHA complexes of different concentrations had lower IgE binding capacity (C-0.3:37.38 ± 0.61; C-0.5:34.89 ± 0.80; C-1:35.69 ± 0.61%) compared with that of natural 7S (100%), while the noncovalent 7S-CHA complexes showed concentration-dependent inhibition of IgE binding capacity (N-0.3:57.89 ± 1.23; N-0.5:46.91 ± 1.57; N-1:40.79 ± 0.22%). Both interactions produced binding to known linear epitopes. This study provides the theoretical basis for the CHA application in soybean products to lower soybean allergenicity.

High hydrostatic pressure induced gastrointestinal digestion behaviors of quercetin-loaded casein delivery systems under different calcium concentration.

Casein micelle has a structure of outer hydrophilicity and inner hydrophobicity, its typical digestion characteristic is gastric coagulation. Based on calcium content as the key factor to control this process, high hydrostatic pressure (HHP) was firstly used to modify the micelle structure by mediating the tight connection between casein molecules themselves and with colloidal calcium, then the quercetin-loaded delivery systems were prepared. And in order to investigate the effect of exogenous calcium, calcium chloride was added for digestion. The results indicated that HHP broke the limitation of casein micelles as delivery carriers for hydrophobic components and increased the EE from 51.18 ± 3.07 % to 76.17 ± 3.41 %. During gastric digestion, higher pressure and exogenous calcium synergistically increased the clotting ability and inhibited the release of quercetin. In the small intestine, curds decomposed more slowly under higher pressure and calcium concentration, so the degradation of quercetin was effectively inhibited.

An enhanced grey wolf optimizer boosted machine learning prediction model for patient-flow prediction.

Large and medium-sized general hospitals have adopted artificial intelligence big data systems to optimize the management of medical resources to improve the quality of hospital outpatient services and decrease patient wait times in recent years as a result of the development of medical information technology and the rise of big medical data. However, owing to the impact of several elements, including the physical environment, patient, and physician behaviours, the real optimum treatment effect does not meet expectations. In order to promote orderly patient access, this work provides a patient-flow prediction model that takes into account shifting dynamics and objective rules of patient-flow to handle this issue and forecast patients' medical requirements. First, we propose a high-performance optimization method (SRXGWO) and integrate the Sobol sequence, Cauchy random replacement strategy, and directional mutation mechanism into the grey wolf optimization (GWO) algorithm. The patient-flow prediction model (SRXGWO-SVR) is then proposed using SRXGWO to optimize the parameters of support vector regression (SVR). Twelve high-performance algorithms are examined in the benchmark function experiments' ablation and peer algorithm comparison tests, which are intended to validate SRXGWO's optimization performance. In order to forecast independently in the patient-flow prediction trials, the data set is split into training and test sets. The findings demonstrated that SRXGWO-SVR outperformed the other seven peer models in terms of prediction accuracy and error. As a result, SRXGWO-SVR is anticipated to be a reliable and efficient patient-flow forecast system that may help hospitals manage medical resources as effectively as possible.

The in-vitro digestion behaviors of micellar casein acting as wall materials in spray-dried microparticles: The relationships between colloidal calcium phosphate and the release of loaded blueberry anthocyanins.

Micellar casein (MC) is a natural carrier for delivering various bioactive substances, and its gastrointestinal digestion behavior has an important impact on the loaded materials. Studies have shown that the digestion behavior of MC is dominated by colloidal calcium phosphate (CCP) in micelle structure. In this paper, The MCs with different CCP levels were used as the carriers to prepare spray-dried microparticles loaded with blueberry anthocyanins (ACNs), then the release of ACNs during digestion was investigated. The results found that the microparticles with less CCP showed the faster dissolution and quicker protein hydrolysis, which caused weaker curd ability. The coagulation was believed as the critical issue to influence the digestion and release behaviors. Therefore, lowering CCP resulted in significantly more ACNs released. This study demonstrated the possibility of using CCP levels to control MC digestion behaviors, which can further determine the release of loaded bioactive substances in casein-based delivery systems.

Enhanced rehydration behaviors of micellar casein powder: The effects of high hydrostatic pressure treatments on micelle structures.

Natural micellar casein is generally dried into powdered forms for commercial transportation and storage. However, the poor rehydration ability of micellar casein powder critically limited the potential applications due to its dense cross-linked structures caused by colloidal calcium phosphate (CCP). In this study, micellar casein solutions were exposed to a high hydrostatic pressure (HHP) ranging from 100 to 500 MPa and were then freeze dried to produce powders. The effects on the casein micelle structures and the rehydration characteristics including wetting, dispersion and dissolving were comprehensively investigated. The results showed that HHP could induce smaller micelle sizes and significantly increase the free calcium in the reconstituted solution. It demonstrated that the majority of CCP bridges in casein micelles were dissociated, which produced porous powders with loose structures and thus significantly improved rehydration behaviors. 300 MPa was the pressure level that caused the quickest dispersion process and best solubility. Consequently, HHP has potential to be a novel physical technique to potentially modify the protein higher-order structures as well as improve the corresponding functionalities.

[Case-control study on therapeutic effects of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries].

OBJECTIVE: To observe the effects of Chinese herb of promoting blood circulation to dissipate blood stasis on the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum of patients with mudslide injuries, and investigate the mechanisms of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries. METHODS: Patients with mudslide injuries who were translated from Zhouqu and Chengxian to Lanzhou from 12th August 2010 were divided into two groups (group A and group B). Twenty-five patients in group A, containing 15 males and 10 females, with an average age of (39.0 +/- 3.9) years. According to AIS scoring system, 1 point in 2 cases, 2 points in 3, 3 points in 17 and 4 points in 3. No patients got 5 points. Based on ISS rating system, 16 cases got 16 points or less, 7 cases rated between 16 and 25, only 2 cases were equal to 25 points or more. Another 25 patients were in group B, including 11 males and 14 females, with a mean age of (40.1 +/- 3.6) years; AIS score showed 3 cases got 1 point, 4 got 2 points, 16 got 3 and 2 got 4 points, no patients got 5 points. Patients in group B were divided into three parts by ISS score:15 cases (16 points or less); 9 cases (range 16 to 25 points) and 1 case (25 points or more). All the patients accepted general physical checkup. Eight patients were treated by surgical treatment in group A (3 patients were treated with open reduction plate fixation, 4 patients were treated with debridement BHID, and 1 patient underwent foreign body removal) and 6 cases in group B (1 patient was treated with craniocerebral surgery,2 patients were treated with chest surgery, and 3 patients were treated with soft tissue debridement). All the patients of two groups were treated by support treatment, detumescence treatment and preventing infection, complications. A seven days course of treatment with detumescence analgesic mixture 50 ml p.o. bid, traumatologic cleansing liquid 20 ml ad us, ext 20 to 30 min qid to group A,continuous treatment of two courses. Using immunometric assay to determine serum levels of inflammatory cytokine TNF-alpha, IL-6 at the 2nd, 7th, 14th days after admission. Analysis of data were done with the help of SPSS 16.0 statistic software. RESULTS: There were no statistical differences of TNF-alpha, IL-6 between two groups at the second day after admission, and there were statistical differences at the 7th and 14th days between two groups. There were significant differences of TNF-alpha and IL-6 levels between the 7th day and the 2nd day, the 14th day and 2nd day after admission. CONCLUSION: The Chinese herb of promoting blood circulation to dissipate blood stasis can inhibit the release of inflammatory factor after traumatism.