A sensitive gold nanoflower-based lateral flow assay coupled with gold staining technique for the detection of SARS-CoV-2 antigen.

An enhanced lateral flow assay (LFA) is presented for rapid and highly sensitive detection of acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigens with gold nanoflowers (Au NFs) as signaling markers and gold enhancement to amplify the signal intensities. First, the effect of the morphology of gold nanomaterials on the sensitivity of LFA detection was investigated. The results showed that Au NFs prepared by the seed growth method showed a 5-fold higher detection sensitivity than gold nanoparticles (Au NPs) of the same particle size, which may benefit from the higher extinction coefficient and larger specific surface area of Au NFs. Under the optimized experimental conditions, the Au NFs-based LFA exhibited a detection limit (LOD) of 25 pg mL-1 for N protein using 135 nm Au NFs as the signaling probes. The signal was further amplified by using a gold enhancement strategy, and the LOD for the detection of N protein achieved was 5 pg mL-1. The established LFA also exhibited good repeatability and stability and showed applicability in the diagnosis of SARS-CoV-2 infection.

The pathogenesis of prevalent aerobic bacteria in aerobic vaginitis and adverse pregnancy outcomes: a narrative review.

BACKGROUND: Aerobic vaginitis is a common cause of vaginal discharge in reproductive-age women, increasing the risk of negative pregnancy outcomes such as premature delivery, abortion, premature rupture of membranes and stillbirth. However, the aetiology and pathogenesis of aerobic vaginitis causing negative pregnancy outcomes are still unclear, and there is no unified and standardized treatment method for aerobic vaginitis in the pregnancy period. METHODS: We conducted a literature search of published studies in the English language focusing on aerobic vaginitis and its association with adverse pregnancy outcomes utilizing PubMed and Web of Science from January 1973 through June 2021. The common pathogenic bacteria of aerobic vaginitis during pregnancy, such as group B Streptococcus, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Klebsiella pneumoniae, as well as the related adverse pregnancy outcomes and existing treatments were reviewed. RESULTS: A total of 4534 articles were identified, and 97 studies that had inclusion criteria were subjected to careful review. The pathogenic bacteria of aerobic vaginitis can produce different toxins or affect the local immunity of patients and then lead to the occurrence of infection. Fresh wet mount microscopy is the preferred diagnostic method for aerobic vaginitis. Clindamycin is a common antibiotic used for aerobic vaginitis in pregnant women. The use of products combining probiotics has achieved excellent treatment success. CONCLUSIONS: Future research in this field can provide insights regarding the mechanism of aerobic vaginitis-induced adverse pregnancy outcomes in humans and ways to prevent their occurrence.

Aerobic vaginitis is an infection of the vagina that increases the risk of negative pregnancy outcomes. The aetiology and pathogenesis of aerobic vaginitis causing negative pregnancy outcomes are still unclear. This paper reviews the common pathogenic bacteria of aerobic vaginitis during pregnancy, and the related adverse pregnancy outcomes. We also review the existing treatment. Currently, it is believed that the microflora in aerobic vaginitis is composed of commensal aerobic microorganisms of intestinal origin, and the most frequently encountered bacteria are group B Streptococcus, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Klebsiella pneumoniae. The pathogenic bacteria of aerobic vaginitis can produce different toxins or affect the local immunity of patients and then lead to the occurrence of infection. Fresh wet mount microscopy is the preferred diagnostic method for aerobic vaginitis. Clindamycin is a common antibiotic used for aerobic vaginitis in pregnant women. The use of products combining probiotics has achieved excellent treatment success. This study provides a reference for future research and early diagnosis and treatment during pregnancy. Future research in this field can provide insights regarding the mechanisms of aerobic vaginitis-induced adverse pregnancy outcomes in humans and ways to prevent their occurrence.

Upconverting Nanocarriers Enable Triggered Microtubule Inhibition and Concurrent Ferroptosis Induction for Selective Treatment of Triple-Negative Breast Cancer.

Despite the resistance of triple-negative breast cancer (TNBC) to targeted hormone therapy, the discovery of azobenzene combretastatin A4 (Azo-CA4) provides therapeutic opportunities for TNBC. Here, Azo-CA4 was loaded in upconverting nanocarriers that could convert near-infrared (NIR) light to UV light to activate Azo-CA4. Upon irradiation, Azo-CA4-loaded nanocarriers significantly reduced the viability of TNBC cells via both apoptosis and ferroptosis. The former was induced by photoisomerization of Azo-CA4, accompanied by microtubule breakdown and cell cycle arrest at G2/M phase. The latter was caused by the UV light-induced reduction of Fe3+ to Fe2+ that facilitates the peroxidation of tailored lipids. The cooperation between apoptosis and ferroptosis in eliminating TNBC was demonstrated in a xenograft mice model in terms of histological staining, tumor growth inhibition, and animal survival. Since the NIR light is only applied to the tumor site, the adverse effects of such triggered nanocarriers to the healthy organs are negligible.

Nanomaterial-enhanced chemiluminescence reactions and their applications.

Chemiluminescence (CL) analysis is a trace analytical method that possesses advantages including high sensitivity, wide linear range, easy operation, and simple instruments. With the development of nanotechnology, many nanomaterial (NM)-enhanced CL systems have been established in recent years and applied for the CL detection of metal ions, anions, small molecules, tumor markers, sequence-specific DNA, and RNA. This review summarizes the research progress of the nanomaterial-enhanced CL systems the past five years. These CL reactions include luminol, peroxyoxalate, lucigenin, ultraweak CL reactions, and so on. The CL mechanisms of the nanomaterial-enhanced CL systems are discussed in the first section. Nanomaterials take part in the CL reactions as the catalyst, CL emitter, energy acceptor, and reductant. Their applications are summarized in the second section. Finally, the challenges and opportunities are discussed.

Cationic liposome-triggered luminol chemiluminescence reaction and its applications.

Liposomes are spherical phospholipid bilayer vesicles. In the present study, we found that cationic liposomes made by (2,3-dioleoyloxy-propyl)-trimethylammonium (DOTAP) could enhance the luminol-H2O2 chemiluminescence (CL) reaction. Mechanism studies showed that the positive charge on the surface of liposomes plays an important role in the CL process. We speculated that the cationic liposomes with quaternary ammonium groups on the surface may be capable of catalyzing the decomposition of H2O2 leading to the formation of oxygen-related free radicals including ˙OH, 1O2, and O2˙-. The luminol anions tend to move close to the surface of the cationic liposomes and then to be oxidized by the oxidizing radical species which may be around the surface of cationic liposomes forming excited-state 3-aminophthalate* (3-APA*). When the 3-APA* returns to the ground state, an enhanced CL is observed. In addition, the single-strand DNA (ssDNA) showed a significant inhibition effect on the proposed CL reaction. The CL intensity decreased linearly with an increasing amount of DNA from 0.05 to 2 pmol. We assumed that the binding of ssDNA with cationic liposomes would neutralize the positive charge on the surface of liposomes and inhibit the catalytic activity of DOTAP cationic liposomes. Based on the ssDNA-inhibited luminol-H2O2-cationic liposome CL reaction, simple label-free CL sensing platforms were developed for the detection of sequence-specific DNA related to the hepatitis B virus (HBV) gene and for the detection of ATP (as a model analyte) using an anti-ATP aptamer as the recognition element.

Triggered All-Active Metal Organic Framework: Ferroptosis Machinery Contributes to the Apoptotic Photodynamic Antitumor Therapy.

Nanoscale photodynamic therapy (PDT) is an appealing antitumor modality for which apoptosis is the major mechanism of toxicity induction. It was postulated that the highly reactive singlet oxygen in PDT could deplete glutathione (GSH) and activate ferroptosis, the extent to which could be further manipulated by a redox-responsive nanocarrier. To validate this, a disulfide-bearing imidazole ligand coordinated with zinc to form an all-active metal organic framework (MOF) nanocarrier where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless of light irradiation, the Ce6-loaded nanocarrier caused the depletion of intracellular GSH via the disulfide-thiol exchange reaction in a murine mammary carcinoma cell line (4T1). The GSH depletion further caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement of cytotoxicity that was alleviated by ferroptosis inhibitors. The superior in vivo antitumor efficacy of the all-active nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression and animal survival rate. The coadministration of an iron chelator weakened the antitumor potency of the nanocarrier due to ferroptosis inhibition, which was supported by the fact of tumor growth upsurge and the recovered GPX4 activity. The current work highlights the contribution of ferroptotic machinery to antitumor PDT via an activatable, adaptable, all-active MOF nanocarrier.

In Situ Generation of Prussian Blue with Potassium Ferrocyanide to Improve the Sensitivity of Chemiluminescence Immunoassay Using Magnetic Nanoparticles as Label.

Using magnetic nanoparticles (MNPs) as a label in immunoassay (IA) possesses advantages such as high specific surface area, simple modification process. However, the catalytic activity of MNPs is low, which limits their applications in IA. The present study found it interesting that potassium ferrocyanide reacts with MNPs, leading to the in situ generation of Prussian blue. The produced Prussian blue shows high catalytic activity on a luminol chemiluminescent (CL) reaction. Therefore, a simple and sensitive immunoassay for rabbit IgG (rIgG) as model analyte using MNPs as label was developed. The CL intensity had a linear increase with the concentration of rIgG that ranged from 0.625 to 20 ng mL-1. The limit of detection was calculated to be 0.59 ng mL-1. In addition, the applicability of this method was evaluated using the standard addition method. The recovery ranged from 80.0% to 115.0%. What's more, the proposed CLIA method based on in situ generation of Prussian blue with MNPs was also applied to the detection of carcinoembryonic antigen (CEA) and hepatitis B virus (HBV)-related sequence-specific DNA. The LOD for the detection of CEA and sequence-specific DNA was estimated to be 0.28 ng mL-1 and 0.044 pmol, respectively.

Aerobic vaginitis in late pregnancy and outcomes of pregnancy.

The purpose of this study was to investigate the risk factors and pregnancy outcomes for aerobic vaginitis (AV) in late pregnancy. A total of 624 pregnant women who were treated in the perinatal unit at Tianjin Medical University General Hospital and 365 nonpregnant women who were evaluated at a health management center from January 2015 to June 2016 were recruited for this case-control study. A questionnaire covering personal hygiene habits and sociodemographic factors was administered to pregnant women to analyze risk factors for AV. Bacterial vaginosis, AV, vulvovaginal candidiasis, and Trichomonas vaginitis were scored according to standardized definitions. Pregnancy outcomes were followed up and recorded. The chi-square test and univariate and multivariate logistic regression analyses were used for statistical evaluation. The prevalence of vaginal infection in pregnant and nonpregnant women were 27.9% and 15.3%, respectively (P < 0.05). AV was identified more frequently in pregnant women than in nonpregnant women (4.2% vs. 1.4%; P < 0.05). A history of vaginal infection within 1 year (odds ratio [OR] = 3.219, 95% confidence interval [CI] 1.103-9.346) and external hemorrhoids (OR = 11.233, 95% CI 4.647-27.155) were independent risk factors for AV during pregnancy. A higher incidence of premature rupture of membranes (PROM) was significantly associated with AV (P < 0.05). AV is common in late pregnancy. Clinicians should pay more attention to vaginal microbiota evaluations during pregnancy.

Factors affecting residual/recurrent cervical intraepithelial neoplasia after cervical conization with negative margins.

To identify factors for predicting residual or recurrent cervical intraepithelial neoplasia (CIN) after cervical conization with negative margins. A total of 172 patients with histologically verified high-grade squamous intraepithelial lesions who underwent conization with negative margins were recruited at the General Hospital of Tianjin Medical University from December 2006 to January 2016. Follow-up comprised clinical examination, a liquid-based cytology test, a human papillomavirus (HPV) DNA genotyping test, colposcopy assessment, and if indicated, colposcopy-directed punch biopsy. The Kaplan-Meier method was used to analyze the median recurrent time, whereas log-rank tests and Cox regression models were used to determine the predictors of residual/recurrent CIN. Fourteen residual/recurrent cases (8.1%) were identified in 172 patients. In univariate analysis, cytologic abnormalities on follow-up (P = .000), conization method (P = .017), HPV positivity at any visit (P = .000), persistent HPV infection postconization (P = .000), persistent infection with the same HPV genotype (P = .000), and HPV positivity at 18 months after conization (P = .000) were predictive factors of residual/recurrent CIN. The results of multivariate analysis further revealed that persistent HPV infection postconization (P = .035), HPV positivity at 18 months after conization (P = .017), and cytologic abnormalities on follow-up (P = .000) had an increased risk of residual/recurrent CIN. During follow-up, patients with persistent HPV infection or cytologic abnormalities were at high risk of residual/recurrent CIN and should be identified for close surveillance and monitoring. Meanwhile, patients with HPV who became negative within 18 months after treatment had a low risk of recurrence.

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy.

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Improvement of mimetic peroxidase activity of gold nanoclusters on the luminol chemiluminescence reaction by surface modification with ethanediamine.

Peroxidase is a commonly used catalyst in luminol-H2 O2 chemiluminescence (CL) reactions. Natural peroxidase has a sophisticated separation process, short shelf life and unstable activity, therefore it is important to develop peroxidases that have both high catalytic activity and good stability as alternatives to the natural enzyme. Gold nanoclusters (Au NCs) are an alternative peroxidase with catalytic activity in the luminol-H2 O2 CL reaction. In the present study, ethanediamine was modified on the surface of Au NCs forming cationic Au NCs. The zeta potential of the cationic Au NCs maintained its positive charge when the pH of the solution was between 4 and 9. The cationic Au NCs showed higher catalytic activity in the luminol-H2 O2 CL reaction than did unmodified Au NCs. A mechanism study showed that the better performance of cationic Au NCs may be attributed to the generation of 1 O2 on the surface of cationic Au NCs and a positive surface charge, for better affinity to luminol. Cationic Au NC, acting as a peroxidase mimic, has much better stability than horseradish peroxidase over a wide range of temperatures. We believe that cationic Au NCs may be useful as an artificial peroxidase for a wide range of potential applications in CL and bioanalysis.

Risk factors, microbiology and management of infected lymphocyst after lymphadenectomy for gynecologic malignancies.

OBJECTIVE: To evaluate risk factors, microbiology and management of infected lymphocysts in patients undergoing systemic lymphadenectomy for gynecological cancer. METHODS: Patients with gynecological cancer who developed postoperative lymphocysts after lymphadenectomy were enrolled between January 2009 and June 2017. The clinical data of infected lymphocysts were analyzed and compared with non-infected lymphocysts. Multivariate analysis of risk factors, the microbiology and therapeutic strategies for infected lymphocysts were also evaluated. RESULTS: A total of 115 patients out of 619 developed postoperative lymphocysts, the incidence of infected lymphocysts was 4.36%. Infected lymphocysts were more frequently found in patients with combined pelvic and para aortic lymphadenectomy, higher number of resected pelvic lymph nodes, lower level of postoperative serum hemoglobin and higher proportion of neutropenia. The median diameter of infected lymphocysts was significantly larger than non-infected (71.89 vs 38.47 mm, P < 0.001) and a large size (diameter over 60 mm) was identified as an independent risk factor for infected lymphocysts (OR = 3.933, P = 0.017). The microbiology of infected lymphocysts includes gram-positive cocci, gram-negative bacillus and anaerobic bacteria. Percutaneous catheter drainage was successfully performed in 20 patients with infected lymphocysts. 16 of 19 patients with large lymphoceles received combined antibiobics and PCD therapy and showed clinical remission in all cases. Patients with large size infected lymphocysts who received combined therapy experienced a significantly shorter treatment period and lower recurrent rate than those with only antibiotics (P = 0.046, P = 0.018). CONCLUSIONS: The current study demonstrated that a diameter over 60 mm was an independent risk factor for infected lymphocysts. The predominant bacteria originated from the urogenital or skin flora. The combination of PCD with appropriate antibiotics was a convenient and effective therapeutic strategy resulting in a high success rate.

Imidazole-Bearing Polymeric Micelles for Enhanced Cellular Uptake, Rapid Endosomal Escape, and On-demand Cargo Release.

The complex design of multifunctional nanomedicine is beneficial to overcome the multiple biological barriers of drug delivery, but it also presents additional hurdles to clinical translation (e.g., scaling-up and quality control). To address this dilemma, we employed a simple imidazole-bearing polymer micelle for enhanced cellular uptake, facilitated endosomal escape, and on-demand release of a model drug, SN-38. The micelles were crosslinked by the reversible imidazole/Zn2+ coordination with a drug loading of ca. 4% (w/w) and a diameter less than 200 nm. Under mimicked tumor microenvironment (pH 6.8), the surface charge of micelles reversed from negative to positive, leading to enhanced micelles uptake by model 4T1 cells. Such effect was verified by fluorescent labelling of micelles. Compared to imidazole-free nanocarriers, the charge-reversal micelles delivered significantly more SN-38 to 4T1 cells. Due to the proton sponge effect, imidazole-bearing micelles could rapidly escape from endosomes compared to the control micelles, as evidenced by the kinetic analysis of micelle/endosome co-localization. The coordination crosslinking also enabled the acid-triggered drug release. This work provides a "three birds with one stone" approach to achieve the multifunctionality of nanocarriers without complicated particle design, and opens new avenues of advancing nanomedicine translation via simple tailored nanocarriers.

Analysis of clinical factors correlated with the accuracy of colposcopically directed biopsy.

PURPOSE: Many factors affect the accuracy of colposcopically directed biopsy (CDB). This study aimed to compare the histological results of CDB with those of cone specimens and to determine clinical factors associated with the accuracy of CDB in defining the extent and severity of cervical intraepithelial neoplasia. METHODS: We studied 513 patients diagnosed with cervical intraepithelial neoplasia by CDB who underwent conization between September 2012 and December 2016. We retrospectively evaluated the agreement between histological results on biopsies and cone specimens and analyzed factors influencing the accuracy of the results. RESULTS: The overall agreement between the histological results on biopsy and the corresponding cone specimens was 74.1%; underestimation occurred in 6.4% of cases. The agreement between histological results on biopsy and cone specimen was 54.5% for low-grade lesions, 78.2% for high-grade lesions, and 28.9% for microinvasive cervical cancer. The overall agreement between high-grade cytology and the final histological diagnosis was 86.7%. By univariate analysis, patient age (p = 0.026), menopausal status (p = 0.018), type of transformation zone (p = 0.003), number of biopsies (p = 0.002), and cone width (p = 0.015) were found to be associated with the accuracy of CDB. However, multivariate logistic regression revealed that cone width (p = 0.044) was the only independent factor correlated with CDB accuracy. CONCLUSIONS: Our data suggest that old age (≥50), postmenopausal status, and transformation zone type 3 might be positively associated with the under-diagnosis of CDB. Three or more biopsies and cone width ≥21 mm might improve CDB accuracy. However, cone width was the only independent factor correlated with CDB accuracy.

Observation of intrinsic emission in ß-BiNbO4 available for excitation of both UV light and high energy irradiation.

ß-BiNbO4 with a high temperature triclinic form was prepared via a high-temperature solid-state reaction ceramic method. Structural refinement and surface characteristic studies were performed. The optical absorption, and electronic calculation of the band structures and density of states were also studied. ß-BiNbO4 ceramic has an indirect transition with a band energy of 3.05 eV. The valence band is dominated by O-2p states whereas the conduction band has predominantly Nb 4d and Bi 6s character. The intrinsic luminescence properties of ß-BiNbO4 were reported, and present a blue emission band peak at 435 nm under the excitation of UV light. The ß-BiNbO4 ceramic presents scintillation properties under high energy irradiation. The luminescence was studied via the combinations of the color centers, band calculation and energy transfer from NbO6 to Bi(3+) in the lattices. The thermal quenching and activation energy for the luminescence were reported. ß-BiNbO4 has potential applications in photoluminescence and scintillation materials.

Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers.

Poor aqueous solubility, potential degradation, rapid metabolism and elimination lead to low bioavailability of pleiotropic impotent curcumin. Herein, we report two types of acid-responsive polymeric micelles where curcumin was encapsulated via both covalent and non-covalent modes for enhanced loading capacity and on-demand release. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a hydrazone linker, generating two conjugates differing in architecture (single-tail versus double-tail) and free curcumin was encapsulated therein. The two micelles exhibited similar hydrodynamic size at 95 ± 3 nm (single-tail) and 96 ± 3 nm (double-tail), but their loading capacities differed significantly at 15.0 ± 0.5% (w/w) (single-tail) and 4.8 ± 0.5% (w/w) (double-tail). Under acidic sink conditions (pH 5.0 and 6.0), curcumin displayed a faster release from the single-tail nanocarrier, which was correlated to a low IC50 of 14.7 ± 1.6 (µg mL(-1)) compared to the value of double-tail micelle (24.9 ± 1.3 µg mL(-1)) in HeLa cells. The confocal imaging and flow cytometry analysis demonstrated a superior capability of single-tail micelle for intracellular curcumin delivery, which was a consequence of the higher loading capacity and lower degree of mPEG surface coverage. In conclusion, the dual loading mode is an effective means to increase the drug content in the micellar nanocarriers whose delivery efficiency is highly dependent on its polymer-drug conjugate architecture. This strategy offers an alternative nanoplatform for intracellularly delivering impotent hydrophobic agents (i.e. curcumin) in an efficient stimuli-triggered way, which is valuable for the enhancement of curcumin's efficacy in managing a diverse range of disorders.

Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery.

Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (µg mL(-1)). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (µg mL(-1)), whereas the IC50 of control micelles was 41.0 ± 2.4 (µg mL(-1)). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

Analysis of the Risk Factors for Aerobic Vaginitis: A Case-Control Study.

AIMS: Aerobic vaginitis (AV) is a newly defined clinical entity which may interfere with women's reproductive health and have negative effects on pregnancy. This study was to identify the risk factors for AV. METHODS: Participants in this case-control study included healthy women and women with AV. All participants completed a standardized questionnaire covering sociodemographic factors, sexual behaviors, personal hygiene habits and health behaviors. Uni- and multivariate logistic regression analyses were used for statistical evaluation. RESULTS: A total of 290 women of reproductive age were enrolled. In the multivariate analysis, unmarried status (odds ratio [OR] 2.606, 95% confidence interval [CI] 1.257-5.402), use of an intrauterine device (OR 4.989, 95% CI 1.922-12.952), long-term use of antibiotics (OR 11.176, 95% CI 1.363-91.666) and frequent vaginal douching (OR 4.689, 95% CI 1.363-16.135) were independent risk factors for AV. On the contrary, consistent condom use (OR 0.546, 95% CI 0.301-0.991) and college-level education or above (OR 0.255, 95% CI 0.131-0.497) were independent protective factors. CONCLUSION: Measures that may be considered to prevent AV include enhancing education to improve women's knowledge related to reproductive health, especially unmarried women, encouraging them to consistently use condoms as a contraceptive method, to avoid long-term use of antibiotics and to stop frequent vaginal douching. © 2015 S. Karger AG, Basel.

Diagnostic and therapeutic advancements for aerobic vaginitis.

BACKGROUND: Aerobic vaginitis (AV) is a newly defined clinical entity that is distinct from candidiasis, trichomoniasis and bacterial vaginosis (BV). Because of the poor recognition of AV, this condition can lead to treatment failures and is associated with severe complications, such as pelvic inflammatory disease, infertility, preterm birth and foetal infections. OBJECTIVE: This review describes the diagnosis and treatment of AV and the relationship between AV and pregnancy. RESULTS: The characteristics of AV include severely depressed levels of lactobacilli, increased levels of aerobic bacteria and an inflamed vagina. The diagnosis is made by microscopy on wet mounts of fresh vaginal fluid, and some distinct clinical features are recognized. Vaginal suppositories that contain kanamycin or clindamycin have shown curative effects in nonpregnant women. Additionally, the application of topical probiotics can restore the vaginal flora and reduce the recurrence of AV. Clindamycin vaginal suppositories and probiotics may be a better choice for gravida with AV than metronidazole. AV requires prompt attention, and the early diagnosis and treatment of AV during pregnancy significantly improves perinatal outcomes. CONCLUSION: Further research is needed to define the pathogenesis, diagnostic criteria and standard treatment guidelines for AV.

Acid-responsive polymeric nanocarriers for topical adapalene delivery.

PURPOSE: The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. METHODS: The anti-acne agent, adapalene, was encapsulated in acid-responsive polymer (Eudragit® EPO) nanocarriers via nanoprecipitation. The nanocarriers were characterized in terms of particle size, surface morphology, drug-carrier interaction, drug release and permeation. RESULTS: Adapalene experienced a rapid release at pH 4.0 in contrast to that at pH 5.0 and 6.0. The permeation study using silicone membrane revealed a significant higher drug flux from the nanocarrier (6.5 ± 0.6 µg.cm(-2).h(-1)) in comparison to that (3.9 ± 0.4 µg.cm(-2).h(-1)) in the control vehicle (Transcutol®). The in vitro pig skin tape stripping study showed that at 24 h post dose-application the nanocarrier delivered the same amount of drug to the stratum corneum as the positive control vehicle did. CONCLUSIONS: The acid-responsive nanocarriers hold promise for efficient adapalene delivery and thus improved acne therapy.