Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice.

Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted with CD34+ hematopoietic stem cells, followed by mucosal challenge with an HIV-1 infectious molecular clone expressing the envelope of a tier 2 resistant HIV-1 strain. Treatment with anti-V1V2 mAb 2158 or anti-V3 mAb 2219 did not prevent infection, but V3 mAb 2219 displayed a superior potency compared to V1V2 mAb 2158 in reducing virus burden. While these mAbs had no or weak neutralizing activity and elicited undetectable levels of antibody-dependent cellular cytotoxicity (ADCC), V3 mAb 2219 displayed a greater capacity to bind virus- and cell-associated HIV-1 envelope and to mediate antibody-dependent cellular phagocytosis (ADCP) and C1q complement binding as compared to V1V2 mAb 2158. Mutations in the Fc region of 2219 diminished these effector activities in vitro and lessened virus control in humanized mice. These results demonstrate the importance of Fc functions other than ADCC for antibodies without potent neutralizing activity.

Promising response of dabrafenib, trametinib, and osimertinib combination therapy for concomitant BRAF and EGFR-TKI resistance mutations.

Despite the initial promise of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in effectively combating tumor growth, the majority of patients with advanced non-small cell lung cancers (NSCLCs) inevitably develop resistance to these treatments. An infrequent genetic mutation known as BRAFV600E has been identified as a contributing factor to the emergence of acquired resistance to EGFR-TKIs. Genetic alterations in BRAF, particularly V600E, contribute to resistance to osimertinib. However, a combination therapy involving osimertinib, dabrafenib (a BRAF inhibitor), and trametinib has shown effectiveness in overcoming BRAF V600E-mediated resistance in advanced lung adenocarcinoma. This treatment regimen holds promise for similar cases. In our case report, the combination of osimertinib, dabrafenib, and trametinib effectively overcame osimertinib resistance and resulted in sustained partial remission.

Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Status of research on the development and regeneration of hair follicles.

Hair loss, or alopecia, is a prevalent condition in modern society that imposes substantial mental and psychological burden on individuals. The types of hair loss, include androgenetic alopecia, alopecia areata, and telogen effluvium; of them, androgenetic alopecia is the most common condition. Traditional treatment modalities mainly involve medical options, such as minoxidil, finasteride and surgical interventions, such as hair transplantation. However, these treatments still have many limitations. Therefore, exploring the pathogenesis of hair loss, specifically focusing on the development and regeneration of hair follicles (HFs), and developing new strategies for promoting hair regrowth are essential. Some emerging therapies for hair loss have gained prominence; these therapies include low-level laser therapy, micro needling, fractional radio frequency, platelet-rich plasma, and stem cell therapy. The aforementioned therapeutic strategies appear promising for hair loss management. In this review, we investigated the mechanisms underlying HF development and regeneration. For this, we studied the structure, development, cycle, and cellular function of HFs. In addition, we analyzed the symptoms, types, and causes of hair loss as well as its current conventional treatments. Our study provides an overview of the most effective regenerative medicine-based therapies for hair loss.

The relationship between dysphagia and frailty among Chinese hospitalized older patients: a serial mediation model through self-perceived oral health and self-reported nutritional status.

BACKGROUND: Frailty contributes to adverse outcomes in older adults and places a heavy burden on healthcare resources. Dysphagia is associated with frailty, but the mechanisms by which dysphagia affects frailty in older adults are unclear. This study aimed to investigate a serial mediating effect of self-perceived oral health and self-reported nutritional status in the relationship between dysphagia and frailty among hospitalized older patients in China. METHODS: This cross-sectional study included 1200 patients aged ≥ 65 years in the Department of Geriatrics, Shaanxi Provincial People's Hospital. A structured face-to-face interview was used to survey the following questionnaires: General Information Questionnaire, Tilburg Frailty Indicators (TFI), Eating Assessment Tool-10 (EAT-10), 30mL Water Swallow Test (WST), Geriatric Oral Health Assessment Index (GOHAI), and Short-Form Mini-Nutritional Assessment (MNA-SF). A total of 980 participants with complete data were included in the analysis. Statistical analysis was performed using SPSS 26.0 and Amos 28.0 software. Spearman's correlation analysis was used for correlation analysis of study variables. The results of the multivariate linear regression analysis for frailty were used as covariates in the mediation analysis, and the structural equation model (SEM) was used to analyze the mediating effects among the study variables. RESULTS: Dysphagia, self-perceived oral health, self-reported nutritional status, and frailty were significantly correlated (P<0.001). Dysphagia was found to directly affect frailty (ß = 0.161, 95%CI = 0.089 to 0.235) and through three significant mediation pathways: (1) the path through self-perceived oral health (ß = 0.169, 95%CI = 0.120 to 0.221), accounting for 36.98% of the total effect; (2) the path through self-reported nutritional status (ß = 0.050, 95%CI = 0.023 to 0.082), accounting for 10.94% of the total effect; (3) the path through self-perceived oral health and self-reported nutritional status (ß = 0.077, 95%CI = 0.058 to 0.102), accounting for 16.85% of the total effect. The total mediation effect was 64.77%. CONCLUSIONS: This study indicated that dysphagia was significantly associated with frailty. Self-perceived oral health and self-reported nutritional status were serial mediators of this relationship. Improving the oral health and nutritional status of hospitalized older patients may prevent or delay the frailty caused by dysphagia.

DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.

The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles.

Silica nanoparticles (SiNPs) are widely used in the biomedical field and can enter the central nervous system through the blood-brain barrier, causing damage to hippocampal neurons. However, the specific mechanism remains unclear. In this experiment, HT22 cells were selected as the experimental model in vitro, and the survival rate of cells under the action of SiNPs was detected by MTT method, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and adenosine triphosphate (ATP) were tested by the kit, the ultrastructure of the cells was observed by transmission electron microscope, membrane potential (MMP), calcium ion (Ca2+) and apoptosis rate were measured by flow cytometry, and the expressions of mitochondrial functional protein, mitochondrial dynein, mitochondrial autophagy protein as well as apoptosis related protein were detected by Western blot. The results showed that cell survival rate, SOD, CAT, GSH-Px, ATP and MMP gradually decreased with the increase of SiNPs concentration, while intracellular ROS, Ca2+, LDH and apoptosis rate increased with the increase of SiNPs concentration. In total cellular proteins,the expressions of mitochondrial functional proteins VDAC and UCP2 gradually increased, the expression of mitochondrial dynamic related protein DRP1 increased while the expressions of OPA1 and Mfn2 decreased. The expressions of mitophagy related proteins PINK1, Parkin and LC3Ⅱ/LC3Ⅰ increased and P62 gradually decreased, as well as the expressions of apoptosis related proteins Apaf-1, Cleaved-Caspase-3, Caspase-3, Caspase-9, Bax and Cyt-C. In mitochondrial proteins, the expressions of mitochondrial dynamic related proteins DRP1 and p-DRP1 were increased, while the expressions of OPA1 and Mfn2 were decreased. Expressions of mitochondrial autophagy associated proteins PINK1, Parkin, LC3II/LC3I increased, P62 decreased gradually, as well as the expressions of apoptosis related proteins Cleaved-Caspase-3, Caspase-3, and Caspase-9 increased, and Cyt-C expressions decreased. To further demonstrate the role of ROS and DRP1 in HT22 cell apoptosis induced by SiNPs, we selected the ROS inhibitor N-Acetylcysteine (NAC) and Dynamin-related protein 1 (DRP1) inhibitor Mdivi-1. The experimental results indicated that the above effects were remarkably improved after the use of inhibitors, further confirming that SiNPs induce the production of ROS in cells, activate DRP1, cause excessive mitochondrial division, induce mitophagy, destroy mitochondrial function and eventually lead to apoptosis.

Unraveling the role of microRNAs: potential biomarkers for gestational diabetes mellitus revealed through RNA sequencing analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) poses significant health risks for both mothers and children, contributing to long-term complications such as type 2 diabetes and cardiovascular disease. This study explores the potential of microRNAs (miRNAs) as biomarkers for GDM by analyzing peripheral blood samples from GDM patients. METHOD: Ten samples, including peripheral blood from 5 GDM patients and 5 controls, were collected to perform the RNA sequencing analysis. Differentially expressed miRNAs were further validated by quantitative real-time polymerase chain reaction. RESULTS: A total of 2287 miRNAs were identified, 229 of which showed differential expression. Validation by qRT-PCR confirmed significant up-regulation of miR-5193, miR-5003-3p, miR-3127-5p, novel-miR-96, miR-6734-5p, and miR-122-5p, while miR-10395-3p was down-regulated. Bioinformatics analyses revealed the involvement of these miRNAs in pathways associated with herpes simplex virus 1 infection. CONCLUSION: This study provides insights into the differential expression of miRNAs in GDM patients and their potential roles in disease pathogenesis. It suggests that the differentially expressed miRNAs could serve as potential biomarkers for GDM, shedding light on the complex molecular mechanisms involved.

[Clinical phenotype and genetic analysis of six Chinese patients affected with Acromicric dysplasia due to variants of FBN1 gene].

OBJECTIVE: To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. METHODS: Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing. RESULTS: All of the six patients had presented with severe short stature (< 3s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c.5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c.5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c.5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c.5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c.5156G>T was rated as a pathogenic variant (PS2+PM1+PM2_Supporting +PM5+PP3). CONCLUSION: All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.

[Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol]. / é«˜æµ·æ‹”åœ°åŒºå¥åº·è¶³æœˆæ–°ç”Ÿå„¿è„‘æ°§ä»£è°¢åŠè„‘ç”µæ´»åŠ¨å·®å¼‚çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.

Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation.

O-GlcNAc transferase (OGT) is the distinctive enzyme responsible for catalyzing O-GlcNAc addition to the serine or threonine residues of thousands of cytoplasmic and nuclear proteins involved in such basic cellular processes as DNA damage repair, RNA splicing, and transcription preinitiation and initiation complex assembly. However, the molecular mechanism by which OGT regulates gene transcription remains elusive. Using proximity labeling-based mass spectrometry, here, we searched for functional partners of OGT and identified interacting protein Dot1L, a conserved and unique histone methyltransferase known to mediate histone H3 Lys79 methylation, which is required for gene transcription, DNA damage repair, cell proliferation, and embryo development. Although this specific interaction with OGT does not regulate the enzymatic activity of Dot1L, we show that it does facilitate OGT-dependent histone O-GlcNAcylation. Moreover, we demonstrate that OGT associates with Dot1L at transcription start sites and that depleting Dot1L decreases OGT associated with chromatin globally. Notably, we also show that downregulation of Dot1L reduces the levels of histone H2B S112 O-GlcNAcylation and histone H2B K120 ubiquitination in vivo, which are associated with gene transcription regulation. Taken together, these results reveal that O-GlcNAcylation of chromatin is dependent on Dot1L.

Whole Genome Resource and Genetic Analysis of Magnaporthe oryzae from Two Field Isolates in Northeast China.

To screen candidate fungal genes that may relate to avirulence genes corresponding to the host resistance genes, we characterized two field isolates of Magnaporthe oryzae that cause rice blast disease, especially in northeast China, and performed whole-genome resequencing of these two isolates. The genome assembly and annotation data was submitted to the National Center for Biotechnology Information database. Our study unveils the predicted fungal effectors of two dominant M. oryzae isolates in northeast China, providing a resource for Avr genes to clone. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

N6-methyladenosine methylation regulatory pattern of pulmonary lymphoepithelioma-like carcinoma based on exosomal transcriptome analysis.

Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare malignancy that lacks specific biomarkers. N6-methyladenosine (m6 A) is the most widespread internal modification of messenger RNA (mRNA), and its dysregulation is involved in the development of many cancers. However, the expression of m6 A genes in pLELC and their roles are unknown. We obtained an exosomal transcriptome data set of patients diagnosed with pLELC and healthy controls using RNA sequencing and identified differentially expressed genes (DEGs) in the two groups using R software. The differential expression of the 37 m6 A genes in the two sets of samples was further analyzed, and receiver operating characteristic (ROC) curves were plotted for each gene to identify their grouping ability. The STRING database was used to construct a protein-protein interaction network for m6 A genes. An mRNA-miRNA regulatory network of m6 A-related DEGs was constructed using the miRNet database, and a prediction score formula was established. A nomogram was constructed based on the candidate m6 A genes and prediction scores. The expression of key genes was determined through the immunohistochemical (IHC) staining of clinical tissue sections. Using ROC curves, nine m6 A genes were revealed to have classification efficacy in both groups of samples. We screened seven m6 A-related DEGs (MAN2C1, HNRNPCL1, FUS, EIF6, DIP2A, COA3, and BUD13) that were beneficial for grouping and constructed nomogram models. Through IHC, we identified FUS and EIF6 as being possibly involved in the occurrence and development of pLELC. The m6 A gene expression patterns in pLELC-derived exosomes were significantly different from those in healthy controls. We screened several key genes to facilitate the development of diagnostic markers for pulmonary lymphoepithelioma.

Novo pathogenic variations of NLRP7 increasing the risk of gestational trophoblastic neoplasia.

Identification of novo mutations of NLRP7 in HM patients. NLRP7 mutations increasing the risk of HM progression.

Cognitive Benefit of a Multidomain Intervention for Older Adults at Risk of Cognitive Decline: A Cluster-Randomized Controlled Trial.

OBJECTIVE: We sought to assess cognitive benefits of a community-based multidomain intervention for improving cognition among older adults at risk of cognitive decline (COMBAT). DESIGN: A two-armed cluster-randomized controlled trial. SETTING AND PARTICIPANTS: Community-dwelling older adults aged 60 years or older and were at risk of cognitive decline (n = 209). INTERVENTION: In this 9-month intervention study, 10 community hospitals in Beijing, China, were randomized (1:1) to receive either a multidomain intervention of meditation, cognitive training, exercise, and nutrition counseling or usual care. The intervention was delivered with weekly 1-hour group training sessions and weekly home homework. MEASUREMENTS: Primary outcome was change in cognition as measured by a composite Z score of seven cognitive tests. Secondary outcomes included subjective cognitive abilities, positive and negative affective experiences, physical activity, and dietary habits. Assessments were administered at baseline, end of the intervention, and 1 year after completing the intervention (1-year follow-up). RESULTS: Immediately after the intervention, the intervention group showed significant enhancement in cognitive performance (p = 0.026). The between-group difference in the Z score of change of cognition was 0.20 (95% CI: 0.053, 0.35), with a Hedges' g of 0.40 (95% CI: 0.29, 0.50). However, this cognitive benefit was not significant at 1-year follow-up. CONCLUSION: This multidomain intervention was effective to improve cognition for at-risk individuals. Long-term effects on cognitive function and individual differences in response to the intervention deserve further investigation.

Coexistence of cryoglobulinemia and ANCA-associated vasculitis in a chronic brucellosis patient -a case report and literature review.

BACKGROUND: The renal involvement of brucellosis is not common. Here we reported a rare case of chronic brucellosis accompanied by nephritic syndrome, acute kidney injury, the coexistence of cryoglobulinemia and antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) superimposed on iliac aortic stent implantation. The diagnosis and treatment of the case are instructive. CASE PRESENTATION: A 49-year-old man with hypertension and iliac aortic stent implantation was admitted for unexplained renal failure with signs of nephritic syndrome, congestive heart failure, moderate anemia and livedoid change in the left sole with pain. His past history included chronic brucellosis and he just underwent the recurrence and completed the 6 weeks of antibiotics treatment. He demonstrated positive cytoplasmic/proteinase 3 ANCA, mixed type cryoglobulinemia and decreased C3. The kidney biopsy revealed endocapillary proliferative glomerulonephritis with a small amount of crescent formation. Immunofluorescence staining revealed only C3-positive staining. In accordance with clinical and laboratory findings, post-infective acute glomerulonephritis superimposed with AAV was diagnosed. The patient was treated with corticosteroids and antibiotics and sustained alleviation of renal function and brucellosis was achieved during the course of a 3-month follow-up. CONCLUSIONS: Here we describe the diagnostic and treatment challenge in a patient with chronic brucellosis related glomerulonephritis accompanied by the coexistence of AAV and cryoglobulinemia. Renal biopsy confirmed the diagnosis of postinfectious acute glomerulonephritis overlapping with ANCA related crescentic glomerulonephritis, which was not ever reported in the literature. The patient showed a good response to steroid treatment which indicated the immunity-induced kidney injury. Meanwhile, it is essential to recognize and actively treat the coexisting brucellosis even when there are no clinical signs of the active stage of infection. This is the critical point for a salutary patient outcome for brucellosis associated renal complications.

Self-Assembly of Glycolipid Epimers: Their Supramolecular Morphology Control and Immunoactivation Function.

Although advances have been made in carbohydrate-based macromolecular self-assembly, harnessing epimers of carbohydrates to perform molecular assembly and further investigating the properties of supramolecular materials remain little explored. Herein, two classes of stereoisomeric glycolipid amphiphiles based on d-N-acetylgalactosamine (GalNAc) are reported, and they can aggregate into ribbon-like structures in the aqueous solution due to amphiphilic property, which allow to obtain glycocalyx-mimicking supramolecular materials. The subtle distinction in glycoside configuration of GalNAc-α-SSA and GalNAc-ß-SSA dictates the different molecular packing in self-assembled structures. Since driven by the distinguishing carbohydrate-carbohydrate interactions, the ribbon-like architectures transform into spherical nanostructures via mixing GalNAc-α-SSA and GalNAc-ß-SSA. The resulting spherical micelles fabricated by blending glycolipid epimers can potentiate the macrophage- and dendritic cell-mediated immune responses in vitro. Such glycolipid epimers will pave the way to create glycocalyx-mimicking immune modulators by incorporating stereochemistry into supramolecular self-assembly.

Vaginal flora during pregnancy and subsequent risk of preterm birth or prelabor rupture of membranes: a nested case-control study from China.

BACKGROUND: The findings of the association of vaginal flora with preterm birth (PTB) or prelabor rupture of membranes (PROM) were conflicts. Moreover, vaginal flora was different by ethnicity and the evidence from China was limited. METHODS: This study was a nested case control study, based on Yiwu birth cohort. We assessed vaginal microbiota in the second or third trimester, using 16S rDNA Amplicon Sequencing and explored the association between the diversity and composition of vaginal flora and PTB or PROM. RESULTS: We finally included 144 pregnant women. In present study, the alpha diversity of TPROM (Term prelabor rupture of membranes) samples was lower than that of full term samples (Chao1 index: P < 0.05). When we further categorized PTB (Preterm birth) into SPB (PTB without PROM) and PPROM (Preterm prelabor rupture of membranes), there was no difference between SPB and full term. In addition, we found that the proportion of PCoA2 in TPROM group was different from that in full term group and preterm group. The difference between groups was significant according to anosim analysis (R = 0.059, P < 0.001). With LEfSe (Linear discriminant analysis Effect Size) analysis, we found that the abundance of Lactobacillus in the vaginal flora of pregnant women with preterm birth was the highest (P = 0.003). CONCLUSION: In Chinese pregnant women, the alpha diversity in TPROM group was significantly lower than that in both PTB and full term group. However, there was no difference between PTB and full term. Lactobacillus was the most abundant in preterm birth group. More studies should be conducted to confirm our findings.

A delayed spontaneous second-trimester tubo-abdominal pregnancy diagnosed and managed by laparotomy in a "self-identified" infertile woman, a case report and literature review.

BACKGROUND: Abdominal pregnancy, a rare form of ectopic pregnancy, is associated with high morbidity and adverse consequences for future fertility. Early recognition and management reduce mortality and allow minimal invasive and conservative treatment. In modern medicine, primitive prevention to unexpected fatal pregnancies is crucial. CASE PRESENTATION: A divorced 33-year-old "self-identified" infertile polycystic ovary woman diagnosed as repeated implantation failure in previous in vitro fertilization with her ex-husband ever presented in surgery department with a history of 15-day abdominal pain, nausea, and vomiting and 3-h worsening abdominal pain. The serum beta-human chorionic gonadotropin value was more than 10,000 m-international units per milliliter. Sonogram findings were significant for the absence of intrauterine gestation; a placenta and well-formed living fetus of second-trimester gestation were seen in the abdomen, accompanied by hemoperitoneum. A unique spontaneously second-trimester tubo-abdominal pregnancy was confirmed in emergent laparotomy by gynecologists, she received a removing of the living fetus, a right total salpingectomy, resection of partial omentum and blood transfusion. The patient recovered uneventfully and her serum beta-human chorionic gonadotropin returned to normal range on the 30th postoperative day, till now, she has weak fertility awareness because of her catastrophic experiences in the unexpected abdominal pregnancy. CONCLUSIONS: This case highlights woman with a previous in vitro fertilization history may be in is a high risk to be delayed or missed in diagnosis in an intended ectopic pregnancy due to a fixed belief in infertility. Educational interventions and contraceptive care should be provided by fertility and healthcare practitioner. The possibility of abdominal pregnancy must always be suspected and dealt with promptly and appropriately by the astute clinician.