The Effects of Pulmonary Artery Catheter on the Short-Term Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A Single-Center Retrospective Study.

Background: Pulmonary artery catheters (PAC) are widely used in patients undergoing off-pump coronary artery bypass (OPCAB) grafting surgery. However, primary data suggested that the benefits of PAC in surgical settings were limited. Therefore, the present study sought to estimate the effects of PAC on the short-term outcomes of patients undergoing OPCAB surgery. Methods: The characteristics, intraoperative data, and postoperative outcomes of consecutive patients undergoing primary, isolated OPCAB surgery from November 2020 to December 2021 were retrospectively extracted. Patients were divided into two groups (PAC and no-PAC) based on PAC insertion status. Data were analyzed with a 1:1 nearest-neighbor propensity score matched-pair in PAC and no-PAC groups. Results: Of the 1004 Chinese patients who underwent primary, isolated OPCAB surgery, 506 (50.39%) had PAC. Propensity score matching yielded 397 evenly balanced pairs. Compared with the no-PAC group (only implanted a central venous catheter), PAC utilization was not associated with improved in-hospital mortality in the entire or matched cohort. Still, the matched cohort showed that PAC utilization increased epinephrine usage and hospital costs. Conclusions: The current study demonstrated no apparent benefit or harm for PAC utilization in OPCAB surgical patients. In addition, PAC utilization was more expensive.

The Effects of Daytime Variation on Short-term Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

OBJECTIVE: To evaluate the effects of time of surgery on the short-term outcomes of patients undergoing off-pump coronary artery bypass grafting (OPCABG). DESIGN: A retrospective cohort study. SETTING: A single large-volume cardiovascular center. PATIENTS: Patients undergoing elective OPCABG between September 2019 and July 2022. INTERVENTIONS: Patients were divided into the following 2 groups according to the start time of surgery: morning (AM group, before 11 AM) and afternoon (PM group, after 11 AM). Propensity-score matching (PSM) with a 1:1 matching ratio was used to create comparable cohorts. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the composite incidence of mortality and morbidities during hospitalization. Secondary endpoints included postoperative bleeding and transfusion, mechanical ventilation duration (MVD), and lengths of stay (LOS) in the intensive care unit (ICU) and hospital. From a consecutive series of 1,039 patients, PSM yielded 317 well-matched pairs. There was no difference in the composite incidence of in-hospital mortality and morbidities between the AM and PM groups (16.4% v 17.4%, p = 0.832). However, patients in the PM group were associated with less postoperative blood loss over the first 24 hours (470 v 540 mL, p = 0.002), decreased MVD (14 v 16 hours, p < 0.001), and shorter LOS in ICU (46 v 68 hours, p = 0.002) compared to patients in AM group. CONCLUSIONS: The current study suggested a lack of relevance regarding the time of surgery with in-hospital mortality and morbidities in patients undergoing OPCABG.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

Immunotherapy of B cell lymphoma with CD22-redirected CAR NK-92 cells.

INTRODUCTION: Chimeric antigen receptor (CAR)-NK cells are considered safer than CAR-T cells due to their short lifetime and production of lower toxicity cytokines. By virtue of unlimited proliferative ability in vitro, NK-92 cells could be utilized as the source for CAR-engineered NK cells. CD22 is highly expressed in B cell lymphoma. The goal of our study was to determine whether CD22 could become an alternative target for CAR-NK-92 therapy against B cell lymphoma. MATERIAL AND METHODS: We first generated m971-BBZ NK-92 that expressed a CAR for binding CD22 in vitro. The expression of CAR was assessed by flow cytometric analysis as well as immunoblotting. The cytotoxicity of the m971-BBZ NK-92 cells towards target lymphoma cells was determined by the luciferase-based cytolysis assay. The production of cytokines in CAR NK-92 cells in response to target cells was evaluated by ELISA assay. Lastly, the cytolytic effect was evaluated by the cytolysis assay mentioned above following irradiation. The level of inhibitory receptor of CAR-expressing cells was assessed by flow cytometry. RESULTS: CD22-specific CAR was expressed on m971-BBZ NK-92 cells successfully. m971-BBZ NK-92 cells efficiently lysed CD22-expressing lymphoma cells and produced large amounts of cytokines after coculture with target cells. Meanwhile, irradiation did not apparently influence the cytotoxicity of m971-BBZ NK-92 cells. Inhibitory receptor detection exhibited a lower level of PD-1 in m971-BBZ NK-92 cells than FMC-63 BBZ T cells after repeated antigen stimulation. CONCLUSIONS: Our data show that adoptive transfer of m971-BBZ NK-92 could serve as a promising strategy for immunotherapy of B cell lymphoma.

Natural Compound 2,2',4'-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T.

Retinoid-related orphan receptor γt (RORγt), a vital transcription factor for the differentiation of the pro-inflammatory Th17 cells, is essential to the inflammatory response and pathological process mediated by Th17 cells. Pharmacological inhibition of the nuclear receptor RORγt provides novel immunomodulators for treating Th17-driven autoimmune diseases and organ transplant rejection. Here, we identified 2,2',4'-trihydroxychalcone (TDC), a natural chalcone derivant, binds directly to the ligand binding domain (LBD) of RORγt and inhibited its transcriptional activation activity. Using three mice models of Th17-related diseases, it was found that the administration of TDC effectively alleviated the disease development of experimental autoimmune encephalomyelitis (EAE), experimental colitis, and skin allograft rejection. Collectively, these results demonstrated TDC targeting RORγt to suppress Th17 cell polarization, as well as its activity, thus, indicating the potential of this compound in treating of Th17-related autoimmune disorders and organ transplant rejection disorders.

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.

The association between heparin sensitivity index and postoperative blood loss in Chinese patients undergoing elective off-pump coronary artery bypass grafting: a single center retrospective study.

BACKGROUND: The heparin sensitivity index (HSI) is closely associated with perioperative ischemic events and increased blood loss in cardiac surgery. Previous studies have produced conflicting results. Therefore, this study aimed to investigate the relationship between HSI and postoperative blood loss specifically in Chinese patients undergoing elective off-pump coronary artery bypass grafting (OPCAB). METHODS: Patients underwent OPCAB between March 2021 and July 2022 were retrospectively included. Enrolled patients were classified into Low-HSI (HSILOW; HSI < 1.3) and Normal-HSI (HSINORM; HSI ≥ 1.3) groups. HSI = [(activated clotting time (ACT) after heparin) - (baseline ACT)] / [loading dose of heparin (IU/kg)]. Primary outcome included postoperative blood loss at 24 h. Secondary outcomes were total postoperative blood loss, transfusion requirement of red blood cell (RBC), fresh frozen plasma (FFP), platelet concentrates (PC), and other complications. RESULTS: We retrospectively analyzed 303 Chinese OPCAB patients. HSILOW group had higher preoperative platelet (PLT) count (221 × 109/L vs. 202 × 109/L; P = 0.041) and platelet crit (PCT) value (0.23% vs. 0.22%; P = 0.040) compared to HSINORM group. Two groups showed no significant differences in postoperative blood loss at 24 h (460 mL vs. 470 mL; P = 0.252), total blood loss (920 mL vs. 980 mL; P = 0.063), RBC transfusion requirement (3.4% vs. 3.1%; P = 1.000), FFP transfusion requirement (3.4% vs. 6.2%; P = 0.380), and other complications. Preoperative high PLT count was associated with low intraoperative HSI value (odds ratio: 1.006; 95% confidence interval: 1.002, 1.011; P = 0.008). CONCLUSIONS: Intraoperative HSI value was not associated with postoperative blood loss in Chinese patients undergoing OPCAB. Preoperative high PLT count was an independent predictor of low intraoperative HSI value.

Dietary Effect of Curcumin on Amino Acid, Fatty Acid, and Volatile Compound Profiles of Chicken Meat.

This study investigated the dietary effect of curcumin (CUR) on amino acid, 5'-nucleotides, fatty acid, and volatile compound profiles of chicken meat. A total of 400 healthy 1-day-old broiler male chicks were divided into 4 groups (n = 10) and fed either a basal diet or a diet with the addition of CUR with concentrations of 100 mg/kg, 150 mg/kg, and 200 mg/kg for 43 days. The results show that the addition of CUR in chicken diets is conducive to promoting the deposition of amino acids and increasing the content of 5'-nucleotides in chicken meat, reducing the contents of saturated fatty acid (SFA) and C20:4 n6 but increasing the ratio between polyunsaturated fatty acid (PUFA) and SFA. In addition, the volatile compound profile shows that the main volatile compounds in chicken meat are aldehydes (including hexanal, heptanal, octanal, and nonanal), with significant increases in their contents observed among chickens in the CUR-intake group. Moreover, it has been found that (E, E)-2,4-nonadienal, trans-2-decenal, benzaldehyde, and trans-2-octenal in chicken meat can significantly increase its overall aroma, and the addition of CUR with 150 mg/kg had the best effect on improving nutritional quality and flavor of chicken meat. This study provides a basis for the comprehensive utilization of CUR as a feed additive with the potential to substitute antibiotics.

The effect of body mass index on short-term outcomes in patients undergoing off-pump coronary artery bypass grafting surgery: a retrospective study from a single cardiovascular center.

OBJECTIVE: This study is designed to investigate the impact of body mass index (BMI) on the short-term outcomes of patients undergoing off-pump coronary artery bypass graft (OPCAB) surgery. METHODS: Data was obtained from 1006 Chinese patients who underwent isolated, primary OPCAB at a high-traffic cardiovascular center during 2020. Subjects were categorized, by BMI, into a low & normal weight (LN) group (BMI < 24 kg/m2), an overweight (OVW) group (24 ≤ BMI < 28 kg/m2), and an obese (OBS) group (BMI ≥ 28 kg/m2). Information pertaining to patients' short-term outcomes (including incidence of mortality and morbidities; duration of postoperative mechanical ventilation; length of stay in the ICU and hospital; postoperative bleeding; etc.) were extracted, and the data from each group were compared. RESULTS: The incidences of in-hospital mortality and morbidities were similar for all three groups. The volume of fluid infusion, postoperative bleeding within 24 h and total bleeding in LN group were higher than those in the OBS group (P < 0.001). The hemoglobin level was lower in the LN group than that in the OBS group (P < 0.001). Duration of mechanical ventilation and length of stay in the ICU in the LN group were longer than those in the OBS group (P < 0.001). CONCLUSIONS: Our results demonstrate that BMI is not significantly related with short-term outcomes in OPCAB patients. However, we suggest that OPCAB patients with low-normal BMI are more susceptible to post-operative blood loss.

Fabrication and characterization of edible Pickering emulsion stabilized by donkey myofibrillar protein.

This study aims to investigate the properties of edible Pickering emulsions (PEs) stabilized by donkey myofibrillar protein (DMP). The DMP was characterized by an atomic force microscope and interfacial tensiometer. The PEs stabilized by DMP were characterized by a confocal laser scanning microscope, rheometer, and lumisizer stability analyzer. The results showed that the DMP particles were spherical nanoparticles with an average size of 143.97 nm. The DMP could reduce the oil-water interfacial tension very well. The emulsifying activity index was below 14.06 m2/g, and the emulsion stability index was up to 93.76% when the DMP concentration was above 10 mg/mL. Increasing the concentration of DMP (5 mg/mL to 25 mg/mL) could decrease the emulsion droplet sizes and fluidity of the PEs and increase the viscoelasticity of the PEs. The increase in the oil-water ratio (1:9 to 5:5) resulted in a larger average emulsion droplet size, reduced fluidity, and enhanced viscoelasticity. The increase in DMP concentration (from 5 mg/mL to 25 mg/mL) and oil-water ratio (from 1:9 to 4:6) improved the physical stability of the PEs. These results may expand the application of DMP and provide new insight into developing edible PEs suitable for the formulation of functional foods.

Adjustable strength and toughness of dual cross-linked nanocellulose films via spherical cellulose as soft-phase.

Nanocellulose films possess numerous merits ascribing to their inherent biocompatibility, non-toxic and biodegradability properties. The potential for practical applications would be improved if their mechanical strength and toughness requirements could be met simultaneously. Herein, dual cross-linked nanocellulose (DC) film was fabricated by the treatments of chemical and physical cross-linking, which was mechanically superior to pure nanocellulose (CNF) films. To further increase the toughness of DC films, spherical cellulose (Sph) was incorporated into DC film (DC-Sph film), and analyzed under different humidity conditions (RH) (from 10 % to 90 %). The changes of functional groups of CNF, DC and DC-Sph films were detected by FTIR and XPS spectrum. The epichlorohydrin and Sph content were optimized, followed by the investigation of RH on the toughness of films. The highest tensile strength (146.6 ± 4.6 MPa) was obtained in DC film at 50 % RH, while the DC-Sph film showed the largest toughness (40.3 ± 3.7 kJ/m2) at 70 % RH. Furthermore, the possible toughening mechanism of DC-Sph film was also discussed.

Correlation between Th17 cells and tumor microenvironment.

Since their identification in 2005, T helper (TH)17 cells have been proposed to play important roles in several human diseases, including various autoimmune conditions, inflammations, allergy, and tumors. Focusing on human studies, we review the current understanding of molecular interactions (IL-1ß, IL-6, IL-23, IL-21 and TGF-ß), the signaling pathway (STAT3→RORγt) and the migration (induced by CCR6/CCL20) that contribute to Th17 differentiation and function in tumor microenvironment. Furthermore, we also make a synthesis of contradictory conclusions as to the roles that these cells are playing in the process of tumourigenesis in order to provide guidance of Th17-targeted therapy in tumors.

Leveraging 16S rRNA data to uncover vaginal microbial signatures in women with cervical cancer.

Microbiota-relevant signatures have been investigated for human papillomavirus-related cervical cancer (CC), but lack consistency because of study- and methodology-derived heterogeneities. Here, four publicly available 16S rRNA datasets including 171 vaginal samples (51 CC versus 120 healthy controls) were analyzed to characterize reproducible CC-associated microbial signatures. We employed a recently published clustering approach called VAginaL community state typE Nearest CentroId clAssifier to assign the metadata to 13 community state types (CSTs) in our study. Nine subCSTs were identified. A random forest model (RFM) classifier was constructed to identify 33 optimal genus-based and 94 species-based signatures. Confounder analysis revealed confounding effects on both study- and hypervariable region-associated aspects. After adjusting for confounders, multivariate analysis identified 14 significantly changed taxa in CC versus the controls (P < 0.05). Furthermore, predicted functional analysis revealed significantly upregulated pathways relevant to the altered vaginal microbiota in CC. Cofactor, carrier, and vitamin biosynthesis were significantly enriched in CC, followed by fatty acid and lipid biosynthesis, and fermentation of short-chain fatty acids. Genus-based contributors to the differential functional abundances were also displayed. Overall, this integrative study identified reproducible and generalizable signatures in CC, suggesting the causal role of specific taxa in CC pathogenesis.

Interactions between microbiota and cervical epithelial, immune, and mucus barrier.

The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts of the female genital tract. It allows sperm and birth passage and hinders the upward movement of microorganisms into a relatively sterile uterus. It is also the predicted site for sexually transmitted infection (STI), such as Chlamydia, human papilloma virus (HPV), and human immunodeficiency virus (HIV). The healthy cervicovaginal microbiota maintains cervical epithelial barrier integrity and modulates the mucosal immune system. Perturbations of the microbiota composition accompany changes in microbial metabolites that induce local inflammation, damage the cervical epithelial and immune barrier, and increase susceptibility to STI infection and relative disease progression. This review examined the intimate interactions between the cervicovaginal microbiota, relative metabolites, and the cervical epithelial-, immune-, and mucus barrier, and the potent effect of the host-microbiota interaction on specific STI infection. An improved understanding of cervicovaginal microbiota regulation on cervical microenvironment homeostasis might promote advances in diagnostic and therapeutic approaches for various STI diseases.

Mixed Vaginitis in the Third Trimester of Pregnancy Is Associated With Adverse Pregnancy Outcomes: A Cross-Sectional Study.

Mixed vaginitis is a complex vaginal dysbiosis that differs from single vaginitis. Vaginitis in the third trimester may lead to adverse maternal and neonatal outcomes. The clinical characteristics, microbiological characteristics, and adverse pregnancy outcomes of mixed vaginitis in late pregnancy are worth studying. Therefore, this study investigated the clinical and microbiological characteristics of vaginitis and adverse pregnancy outcomes of patients with mixed vaginitis. We studied 1,674 women in late pregnancy who attended the Tianjin Medical University General Hospital from November, 2019 to October, 2021. We administered standardized questionnaires, performed vaginal examination and sampling plus microscope examinations, and assessed follow-up pregnancy outcomes. We cultured the vaginal discharge of the patients with mixed vaginitis to isolate pathogens and performed antimicrobial susceptibility tests of the isolated pathogens. For the patients with peripartum infection, we collected a sample to isolate pathogens. Among the 1,674 women, 66 (3.9%) had mixed vaginitis. The independent risk factor for mixed vaginitis in late pregnancy was a history of vaginitis during early and middle pregnancy (OR = 5.637, 95% CI: 3.314-9.580). The signs of vaginal erythema (63.6% vs. 42.0%), yellow discharge (81.8% vs. 59.6%), and malodor (31.8% vs. 18.8%) (P <0.05) were significantly higher in patients with mixed vaginitis than in patients with single vaginitis. Bacterial isolates of the vaginal secretions of patients with mixed bacterial vaginitis were mainly the pathogens of aerobic vaginitis and bacterial vaginosis, such as Gardnerella vaginalis, Streptococcus anginosus, and Staphylococcus epidermidis. Pathogen isolation of the vaginal secretions of patients with mixed fungus and bacteria vaginitis mainly included Candida albicans, followed by S. anginosus, Enterococcus faecalis, Staphylococcus hemolyticus, Staphylococcus aureus, Streptococcus agalactiae and Staphylococcus simulans. Women with mixed vaginitis had an increased incidence and risk of peripartum infections (6.1% vs. 1.4%, P <0.05; OR = 3.985, 95% CI:1.214-13.079). Escherichia coli is the main pathogen that causes peripartum infection. Mixed vaginitis in late pregnancy is characterized by a severe and complex phenotype, complex vaginal dysbiosis, and a long course of vaginal dysbiosis. This can lead to an increased incidence and risk of peripartum infection. Therefore, more attention should be paid to patients with mixed vaginitis in the third trimester of pregnancy.

Baicalin Promotes CNS Remyelination via PPARγ Signal Pathway.

BACKGROUND AND OBJECTIVES: Demyelinating diseases in the CNS are characterized by myelin sheath destruction or formation disorder that leads to severe neurologic dysfunction. Remission of such diseases is largely dependent on the differentiation of oligodendrocytes precursor cells (OPCs) into mature myelin-forming OLGs at the demyelinated lesions, which is defined as remyelination. We discover that baicalin (BA), a natural flavonoid, in addition to its well-known antiinflammatory effects, directly stimulates OLG maturation and CNS myelin repair. METHODS: To investigate the function of BA on CNS remyelination, we develop the complementary in vivo and in vitro models, including physiologic neonatal mouse CNS myelinogenesis model, pathologic cuprizone-induced (CPZ-induced) toxic demyelination model, and postnatal OLG maturation assay. Furthermore, molecular docking, pharmacologic regulation, and transgenic heterozygous mice were used to clarify the target and action of the mechanism of BA on myelin repair promotion. RESULTS: Administration of BA was not only merely effectively enhanced CNS myelinogenesis during postnatal development but also promoted remyelination and reversed the coordination movement disorder in the CPZ-induced toxic demyelination model. Of note, myelin-promoting effects of BA on myelination or regeneration is peroxisome proliferator-activated receptor γ (PPARγ) signaling-dependent. DISCUSSION: Our work demonstrated that BA promotes myelin production and regeneration by activating the PPARγ signal pathway and also confirmed that BA is an effective natural product for the treatment of demyelinating diseases.

Aerobic Vaginitis Diagnosis Criteria Combining Gram Stain with Clinical Features: An Establishment and Prospective Validation Study.

Wet-mount microscopy aerobic vaginitis (AV) diagnostic criteria need phase-contrast microscopy and keen microscopists, and the preservation of saline smears is less common in clinical practice. This research work developed new AV diagnostic criteria that combine Gram stain with clinical features. We enrolled 325 AV patients and 325 controls as a study population to develop new AV diagnostic criteria. Then, an independent group, which included 500 women, was used as a validation population. AV-related microscopic findings on Gram-stained and wet-mount smears from the same participants were compared. The accuracy of bacterial indicators from the two methods was verified by bacterial 16S rRNA V4 sequencing (n = 240). Logistic regression was used to analyse AV-related clinical features. The screened clinical features were combined with Gram-stain microscopic indicators to establish new AV diagnostic criteria. There were no significant differences in the leukocyte counts or the parabasal epitheliocytes (PBC) proportion between the Gram-stain and wet-mount methods (400×). Gram stain (1000×) satisfied the ability to identify bacteria as verified by 16S rRNA sequencing but failed to identify toxic leukocytes. The new criteria included: Lactobacillary grades (LBG) and background flora (Gram stain, 1000×), leukocytes count and PBC proportion (Gram stain, 400×), and clinical features (vaginal pH > 4.5, vagina hyperemia, and yellow discharge). These criteria satisfied the accuracy and reliability for AV diagnosis (Se = 86.79%, Sp = 95.97%, and Kendall's W value = 0.899) in perspective validation. In summary, we proposed an alternative and valuable AV diagnostic criteria based on the Gram stain, which can make it possible to diagnose common vaginitis like AV, BV, VVC, and mixed infections on the same smear and can be available for artificial intelligence diagnosis in the future.

2', 4'-Dihydroxy-2,3-dimethoxychalcone: A pharmacological inverse agonist of RORγt ameliorating Th17-driven inflammatory diseases by regulating Th17/Treg.

Multiple sclerosis, inflammatory bowel disease and organ transplant rejection are related to Th17 cell development and inflammatory respond. RORγt, a specific transcription factor regulating Th17 cell differentiation, is a pivotal target for the treatment of diseases. However, the clinical application of RORγt inverse agonists reported so far has been hindered due to limited efficacy and toxic side effects. Plant-derived natural products with drug-like properties and safety are wide and valuable resources for candidate drug discovery. Herein, structure-based virtual screening was used to find out 2',4'-Dihydroxy-2,3-dimethoxychalcone (DDC), a chalcone derivative rich in plants and food, located in the binding pocket of RORγt and targeted to inhibit RORγt activity. DDC repressed murine Th17 differentiation and promoted Treg differentiation remarkably in a dose-dependent manner. In addition, DDC treatment improved experimental autoimmune encephalomyelitis recovery, ameliorated experimental colitis severity, and prevented graft rejection significantly. Mechanically, DDC indirectly stabilized Foxp3 expression by inhibiting RORγt activity and the expression of its target gene profile in vitro and in vivo, which realized its regulation of Th17/Treg balance. In conclusion, our study provides a scientific basis that DDC, as an inverse agonist of RORγt with simple structure, rich sources, low cost, high efficiency, and low toxicity, has great potential for the development of a novel effective immunomodulator for the treatment of Th17-mediated inflammatory diseases.

Recent Advances in Presentation, Diagnosis and Treatment for Mixed Vaginitis.

Mixed vaginitis is the simultaneous presence of at least two types of vaginitis, contributing to an abnormal vaginal milieu and leading to vaginal symptoms and signs. However, associations between symptoms and the type of mixed vaginitis have not been clearly elucidated, and research on mixed vaginitis is still in the preliminary stage. Therefore, the pathogenic mechanism of mixed vaginitis remains understudied. Mixed vaginitis generally involves the formation of mixed biofilms. The study of polymicrobial interactions and mixed biofilms will provide a new idea for the understanding of mixed vaginitis. Moreover, this review summarizes some effective management and laboratory diagnosis of mixed vaginitis to avoid inappropriate therapy, recurrence, and reinfection. It is of high clinical importance to obtain relevant clinical data to improve clinical knowledge about mixed vaginitis.

Encapsulation of ß-carotene in oleogel-in-water Pickering emulsion with improved stability and bioaccessibility.

ß-carotene (BC) is beneficial for human health. However, the low oxidative stability and bioavailability of hydrophobic BC limit its utilization as supplements in functional foods and pharmaceutical products. Herein a conventional oil-in-water Pickering emulsion (OPEs-1) and an oleogel-in-water Pickering emulsion (OPE-2) were prepared and determined to improve the chemical stability and bioavailability of BC. Cellulose nanocrystals were used as the emulsifier. Oleogel was developed by structuring soybean oil with beeswax. The freezing-thawing (FT) stability and physical stability of the OPEs-2 was improved compared to the OPEs-1. The OPE-2 seemed to be stable against three FT cycles. The OPEs-2 presented higher droplets size than OPEs-1, but they were more stable over a wide range of pH (4.0-8.0) and salt level (0.05-0.60 M). The chemical stability of BC encapsulated in OPEs-2 was higher than that in OPEs-1. For instance, the relative BC concentration decreased from 100% to 71.16%/90.12% in OPE-1/OPE-2 after stored at 25 °C for 15 days. The BC bioaccessibility in OPE-2 (68.17 ± 1.19%) was significantly improved compared with OPE-1 (53.15 ± 1.36%). The results obtained indicated that OPEs-2 was probably an effective delivery system for hydrophobic and indigestible bioactive compounds.