Case report: Successful pregnancy complicated with non-cirrhotic portal hypertension in a lady who suffered from postpartum hemorrhage previously.

RATIONALE: Non-cirrhotic portal hypertension (NCPH) is characterized by the absence of cirrhotic modification of the liver and the patency of the portal and hepatic veins. When compared to the general population, NCPH is associated with an increased risk of maternal and perinatal morbidity and mortality during pregnancy. NCPH was present in the majority (74.1%) of pregnant women with portal hypertension. One (25%) out of every 4 pregnancies was complicated by variceal hemorrhage while pregnant. So far, there is still no consensus in the world about the treatment of this rare condition. PATIENT CONCERNS: We have specifically illustrated a rare instance where the patient was diagnosed with NCPH and hypersplenism at the age of 8 and experienced a 3 L massive hemorrhage during labor induction as a result of her first pregnancy loss due to hypertension. DIAGNOSES AND INTERVENTIONS: The diagnosis of threatened preterm labor with cervical dilatation, gestational diabetes mellitus, massive splenomegaly with hypersplenism, portal vein hypertension, and parenchymal damage of kidney with impaired renal function led to the cesarean delivery of the second pregnancy at 29+3 weeks gestation without splenectomy after been evaluated by multispecialty team. OUTCOMES: She and her child were both in generally good condition 3 months after the operation. LESSONS: Preconception counseling, ongoing follow-up, and monitoring are crucial in pregnant women with NCPH. A multidisciplinary team approach, with timely intervention and intensive monitoring, can help achieve optimal maternal-perinatal outcomes in pregnancies complicated with portal hypertension. Our case provided a successful treatment, but more guidelines for the management of NCPH are needed.

The correlation between changes in gray matter microstructure and cerebral blood flow in Alzheimer's disease.

Objective: To investigate the relationship between changes in cerebral blood flow (CBF) and gray matter (GM) microstructure in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A recruited cohort of 23 AD patients, 40 MCI patients, and 37 normal controls (NCs) underwent diffusional kurtosis imaging (DKI) for microstructure evaluation and pseudo-continuous arterial spin labeling (pCASL) for CBF assessment. We investigated the differences in diffusion- and perfusion-related parameters across the three groups, including CBF, mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA). These quantitative parameters were compared using volume-based analyses for the deep GM and surface-based analyses for the cortical GM. The correlation between CBF, diffusion parameters, and cognitive scores was assessed using Spearman coefficients, respectively. The diagnostic performance of different parameters was investigated with k-nearest neighbor (KNN) analysis, using fivefold cross-validation to generate the mean accuracy (mAcc), mean precision (mPre), and mean area under the curve (mAuc). Results: In the cortical GM, CBF reduction primarily occurred in the parietal and temporal lobes. Microstructural abnormalities were predominantly noted in the parietal, temporal, and frontal lobes. In the deep GM, more regions showed DKI and CBF parametric changes at the MCI stage. MD showed most of the significant abnormalities among all the DKI metrics. The MD, FA, MK, and CBF values of many GM regions were significantly correlated with cognitive scores. In the whole sample, the MD, FA, and MK were associated with CBF in most evaluated regions, with lower CBF values associated with higher MD, lower FA, or lower MK values in the left occipital lobe, left frontal lobe, and right parietal lobe. CBF values performed best (mAuc = 0.876) for distinguishing the MCI from the NC group. Last, MD values performed best (mAuc = 0.939) for distinguishing the AD from the NC group. Conclusion: Gray matter microstructure and CBF are closely related in AD. Increased MD, decreased FA, and MK are accompanied by decreased blood perfusion throughout the AD course. Furthermore, CBF values are valuable for the predictive diagnosis of MCI and AD. GM microstructural changes are promising as novel neuroimaging biomarkers of AD.

Lactobacillus rhamnosus and Lactobacillus casei Affect Various Stages of Gardnerella Species Biofilm Formation.

Bacterial vaginosis (BV) and its recurrence are most commonly associated with the formation of Gardnerella species biofilm. Probiotics are typically used to treat BV; however, the optimal period of Lactobacillus probiotic application in BV treatment remains uncertain. The present study aimed to explore the effects of Lactobacillus rhamnosus and Lactobacillus casei on various stages of biofilm formation in Gardnerella species. The biofilm-forming ability of seven strains, including one Gardnerella vaginalis ATCC 14018 and six clinically isolated Gardnerella species, was determined via gentian violet staining assay. Moreover, the sensitivity of the planktonic and biofilm forms toward metronidazole and clindamycin was assessed via microdilution broth method. L. rhamnosus Xbb-LR-1 and L. casei Xbb-LC-1 were added during various stages of biofilm formation in Gardnerella species and were cocultured for 24 h. The biofilm thickness of each sample was determined via confocal laser scanning microscopy (CLSM). The absolute quantities of Gardnerella species in each sample was obtained via real time polymerase chain reaction method, and the pH value was obtained using a pH indicator paper. Biofilm formation by Gardnerella species in a medium with distinct pH values was observed via gentian violet staining, CLSM, and scanning electron microscopy (SEM). The biofilm increased the resistance of Gardnerella species toward metronidazole and clindamycin. L. rhamnosus added at the initial biofilm formation stage in Gardnerella species exhibited highest inhibitory effect, with a percentage inhibition of 38.17% ± 1.35%. When the pH value of the culture medium was <4.5 or >6.5, ATCC 14018 could hardly form a biofilm; however, at pH ≥4.5 and ≤6.5, it was able to form a stronger biofilm. The amount of biofilm attained maximum value at optical density of 3.29 ± 0.28 (595 nm), pH 5.5, and at 36 h. Biofilm formation increases the resistance of Gardnerella species toward antibiotics. Maintaining an acidic vaginal environment with pH <4.5 and a vaginal microbiota dominated by Lactobacillus remarkably prevents the formation of Gardnerella species biofilm at the initial stage, which further has a significant impact on the treatment and prevention of biofilm-related infections.

Evaluation of the Inhibitory Effects of Lactobacillus gasseri and Lactobacillus crispatus on the Adhesion of Seven Common Lower Genital Tract Infection-Causing Pathogens to Vaginal Epithelial Cells.

Background/Purpose: Lactobacillus colonization is important to maintain urogenital flora stability and prevent pathogenic infection. Different Lactobacillus species have distinct properties and effects on the urogenital flora. To select probiotics that colonize the vagina and provide protection against pathogenic infection, we evaluated the adhesion of five Lactobacillus strains and their inhibitory effects on the adhesion of pathogens to vaginal epithelial cells (VECs). Methods and Materials: (1) Lactobacillus adhesion experiments: VK2/E6E7 and primary VECs were used to evaluate the adhesion of two Lactobacillus gasseri and three Lactobacillus crispatus strains. The adhesion of these five Lactobacillus strains was compared. (2) Adhesion inhibition experiments: The inhibitory effects of the five Lactobacillus strains on the adhesion of pathogens (Gardnerella, Mobiluncus, Candida albicans, Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis) were evaluated by adhesion exclusion, displacement, and competition experiments. Results: (1) Lactobacillus adhesion was stronger in the primary VECs than in the VK2/E6E7 VECs (P < 0.05). The adhesion of the three L. crispatus strains was stronger than that of the two L. gasseri strains (P < 0.05). L. crispatus 4# showed the strongest adhesion. (2) The exclusion, displacement, and competition experiments showed that all five Lactobacillus strains significantly inhibited the adhesion of the seven pathogenic strains to the VECs (P < 0.05). The displacement effect was stronger than the exclusion and competition effects of each Lactobacillus strain. (3) The results of the exclusion, displacement, and competition experiments indicated that L. gasseri 1# showed the strongest adhesion inhibition of C. albicans and S. agalactiae. L. crispatus 3# showed the strongest adhesion inhibition of S. aureus, whereas L. crispatus 4# showed the strongest adhesion inhibition of Gardnerella, Mobiluncus, E. coli, and E. faecalis. Conclusion: The source of the VECs might not affect the selection of the most adhesive Lactobacillus strain. L. crispatus showed stronger VEC adhesion than L. gasseri. The degree of antagonism of the Lactobacillus strains toward the different pathogens varied. This result provides incentives for personalized clinical treatment.

Association Analysis on Recurrence of Bacterial Vaginosis Revealed Microbes and Clinical Variables Important for Treatment Outcome.

To investigate the parameters associated with post-treatment recurrence of bacterial vaginosis (BV), clinical factors and vaginal microbiota were examined and analyzed for BV patients who received standard metronidazole therapy. The variables associated with BV recurrence included clinical factors of past BV history, use of intravaginal device, and D7 Nugent score as well as many microbial genera, with Lactobacillus, Enterococcus, Ureaplasma, and Aerococcus being the top contributors. Co-occurrence network analysis showed that whereas overwhelming majority of interbacterial interactions were positive, negative interactions were present and connected mostly to Lactobacillus, Enterococcus, and to a less extent Ureaplasma, suggesting the importance of interbacterial antagonism for treatment outcome. The patients who were cured and recurrent also exhibited clear differences in the species composition of Lactobacillus: although L. iners remained the dominant species at all time points, L. crispatus, L. gasseri, and L. jensenii displayed apparent differences in relative abundance between the cure and recurrent groups. Based on these results, we developed a 5-component panel comprising Enterococcus, L. crispatus, Ureaplasma, Aerococcus, and L. jensenii for predicting recurrence using D7 data and showed that it generated the specificity, sensitivity, and AUC values of 0.80, 0.66, and 0.73 for the discovery cohort and 0.80, 0.67, and 0.69 for the validation cohort. Our findings highlighted key microbial components for BV recurrence and suggested that they could be used to monitor the treatment outcome.

Recombinant Human IFNα-2b Response Promotes Vaginal Epithelial Cells Defense against Candida albicans.

Classical antifungal drugs have been subjected to restrictions due to drug toxicity, drug resistance, bioavailability, and detrimental drug interactions. Type I interferon (IFN) exerts direct distinct immunostimulatory or immunomodulatory actions; however, little is known regarding the anti-fungal reactions of vaginal epithelial cells (VECs) induced by the type I IFN response. Therefore, in the present study, we evaluated the cytotoxic activity, immunocompetent cytokine responses, and non-B IgG production of the VK2/E6E7 VEC line following recombinant human IFN α-2b (rhIFNα-2b) treatment in response to Candida albicans. When treated with rhIFNα-2b, the production of IL-2, IL-4, and IL-17 were significantly up-regulated compared to the infected control cells (P < 0.05). Our scanning electron microscopy results revealed that C. albicans can invade VECs by inducing both endocytosis and active penetration. RhIFNα-2b was able to transform the VECs into a thallus and stretched pattern, promoting the fusion of filopodia to form a lamellipodium and enhancing the mobility and the repair capacity of the VECs. In addition, rhIFNα-2b could effectively inhibit the adhesion, hyphal formation, and proliferation of C. albicans. Collectively, these responses restored the immune function of the infected VECs against C. albicans in vitro, providing a theoretical basis for this novel treatment strategy.

In vitro activity of farnesol against vaginal Lactobacillus spp.

OBJECTIVE: Farnesol, a quorum-sensing molecule in Candida albicans, can affect the growth of certain microorganisms. The objective of this study was to evaluate the in vitro activity of farnesol against vaginal Lactobacillus spp., which play a crucial role in the maintenance of vaginal health. METHODS: Growth and metabolic viability of vaginal Lactobacillus spp. incubated with different concentrations of farnesol were determined by measuring the optical density of the cultures and with the MTT assay. Morphology of the farnesol-treated cells was evaluated using a scanning electron microscope. In vitro adherence of vaginal Lactobacillus cells treated with farnesol was determined by co-incubating with vaginal epithelial cells (VECs). RESULTS: The minimum inhibitory concentration (MIC) of farnesol for vaginal Lactobacillus spp. was 1500µM. No morphological changes were observed when the farnesol-treated Lactobacillus cells were compared with farnesol-free cells, and 100µM farnesol would reduce the adherence of vaginal Lactobacillus to VECs. CONCLUSION: Farnesol acted as a potential antimicrobial agent, had little impact on the growth, metabolism, and cytomorphology of the vaginal Lactobacillus spp.; however, it affected their adhering capacity to VECs. The safety of farnesol as an adjuvant for antimicrobial agents during the treatment of vaginitis needs to be studied further.

Lactobacillus crispatus Modulates Vaginal Epithelial Cell Innate Response to Candida albicans.

BACKGROUND: Vulvovaginal candidiasis is caused by Candida albicans. The vaginal epithelium, as the first site of the initial stage of infection by pathogens, plays an important role in resisting genital tract infections. Moreover, lactobacilli are predominant members of the vaginal microbiota that help to maintain a normal vaginal microenvironment. Therefore, Lactobacillus crispatus was explored for its capacity to intervene in the immune response of vaginal epithelial cells VK2/E6E7 to C. albicans. METHODS: We examined the interleukin-2 (IL-2), 4, 6, 8, and 17 produced by VK2/E6E7 cells infected with C. albicans and treated with L. crispatus in vitro. The capacity of L. crispatus to adhere to VK2/E6E7 and inhibit C. albicans growth was also tested by scanning electron microscopy (SEM) and adhesion experiments. RESULTS: Compared with group VK2/E6E7 with C. albicans, when treated with L. crispatus, the adhesion of C. albicans to VK2/E6E7 cells decreased significantly by 52.87 ± 1.22%, 47.03 ± 1.35%, and 42.20 ± 1.55% under competition, exclusion, and displacement conditions, respectively. SEM revealed that the invasion of C. albicans into VK2/E6E7 cells was caused by induced endocytosis and active penetration. L. crispatus could effectively protect the cells from the virulence of hyphae and spores of C. albicans and enhance the local immune function of the VK2/E6E7 cells. The concentrations of IL-2, 6, and 17 were upregulated significantly (P < 0.01) and that of IL-8 were downregulated significantly (P < 0.01) in infected VK2/E6E7 cells treated with L. crispatus. The concentration of IL-4 was similar to that of the group VK2/E6E7 with C. albicans (24.10 ± 0.97 vs. 23.12 ± 0.76 pg/ml, P = 0.221). CONCLUSIONS: L. crispatus can attenuate the virulence of C. albicans, modulate the secretion of cytokines and chemokines, and enhance the immune response of VK2/E6E7 cells in vitro. The vaginal mucosa has a potential function in the local immune responses against pathogens that can be promoted by L. crispatus.

Baofukang suppository promotes the repair of vaginal epithelial cells in response to Candida albicans.

Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection predominantly caused by Candida albicans affecting a significant number of women of reproductive age. The Chinese medicine, the Baofukang suppository is widely used in the clinic for its antimicrobial activity and is therefore of great interest as a potential antifungal drug for the prevention of VVC. We evaluated the cytotoxic activity of the Baofukang suppository using the VK2/E6E7 vaginal epithelial cell (VEC) line. When treated with the Baofukang suppository, all of the immunocompetent cytokines and chemokines (e.g., IL-2, IL-4, IL-6, IL-8, and IL-17) by infected VK2/E6E7 cells was statistically up-regulated (P < 0.05), except IL-4 (11.70 ± 1.82 vs. 14.88 ± 4.72, P = 0.343) compared to the infected control cells. The secretion of non-B IgG also exhibited the same trend. Our scanning electron microscopy results revealed that C. albicans can invade VECs by both induced endocytosis and active penetration. The Baofukang suppository could effectively inhibit the adhesion, hyphal formation, and proliferation, as well as notably restore the vaginal epithelial cell morphology, viability, and enhance the local immune function of the VECs. These preliminary results suggest promising antimicrobial properties of the Baofukang suppository, which may be efficacious as an antifungal therapy candidate via up-regulating Th1 cellular immunity, the Th17-axis of the innate immune response, and the secretion of vaginal epithelial-derived IgG. These combined effects collectively restore the immune function of the infected VECs against C. albicans in vitro.

Predictive value of the composition of the vaginal microbiota in bacterial vaginosis, a dynamic study to identify recurrence-related flora.

Bacterial vaginosis (BV) is a highly prevalent disease in women, and increases the risk of pelvic inflammatory disease. It has been given wide attention because of the high recurrence rate. Traditional diagnostic methods based on microscope providing limited information on the vaginal microbiota increase the difficulty in tracing the development of the disease in bacteria resistance condition. In this study, we used deep-sequencing technology to observe dynamic variation of the vaginal microbiota at three major time points during treatment, at D0 (before treatment), D7 (stop using the antibiotics) and D30 (the 30-day follow-up visit). Sixty-five patients with BV were enrolled (48 were cured and 17 were not cured), and their bacterial composition of the vaginal microbiota was compared. Interestingly, we identified 9 patients might be recurrence. We also introduced a new measurement point of D7, although its microbiota were significantly inhabited by antibiotic and hard to be observed by traditional method. The vaginal microbiota in deep-sequencing-view present a strong correlation to the final outcome. Thus, coupled with detailed individual bioinformatics analysis and deep-sequencing technology, we may illustrate a more accurate map of vaginal microbial to BV patients, which provide a new opportunity to reduce the rate of recurrence of BV.