Clinical features, treatment and prognosis of patients with endogenous infectious endophthalmitis.

PURPOSE: To investigate whether the clinical characteristics, treatment and prognosis of endogenous infectious endophthalmitis (EIE) have changed over the past 5 years. METHODS: Retrospectively analyze all articles about EIE published in the PubMed, Web of Science, and Embase databases from 2017 to 2021. RESULTS: A total of 128 patients and 147 eyes (46 left and 60 right) were included in the study. The mean age at diagnosis was 51 ± 19 years. The most common risk factors were diabetes and intravenous drug use. From 2017 to 2021, Klebsiella was the most common pathogenic microorganism (22%), and vitreous culture had the highest positivity rate. The most common complaint was blurred vision. The mean visual acuity (logMAR) at onset was 2.84, and the clinical symptoms were vitreal inflammation and opacity (63%), ocular pain (37%), and conjunctival congestion (36%). The ocular inflammation could be reduced by intraocular antibiotics or vitrectomy. However, the visual prognosis, with a mean logMAR of 2.73; only 50% of the eyes reached a visual acuity level of finger count and above. Changes in diagnostics over the past 5 years have mainly manifested as more diverse microorganism culture methods. In addition to conventional culture methods, PCR, sputum culture and aqueous humour culture are also commonly used for the diagnosis of pathogenic bacteria, improving the positive culture rate and visual prognosis. CONCLUSION: The prognosis of EIE is poor. It is recommended to pay attention to the pathogenic bacteria culture results and accompanying systemic diseases and to diagnose and treat patients as soon as possible.

Short-Chain Fatty Acids Augment Differentiation and Function of Human Induced Regulatory T Cells.

Regulatory T cells (Tregs) control immune system activity and inhibit inflammation. While, in mice, short-chain fatty acids (SCFAs) are known to be essential regulators of naturally occurring and in vitro induced Tregs (iTregs), data on their contribution to the development of human iTregs are sparse, with no reports of the successful SCFAs-augmented in vitro generation of fully functional human iTregs. Likewise, markers undoubtedly defining human iTregs are missing. Here, we aimed to generate fully functional human iTregs in vitro using protocols involving SCFAs and to characterize the underlying mechanism. Our target was to identify the potential phenotypic markers best characterizing human iTregs. Naïve non-Treg CD4+ cells were isolated from the peripheral blood of 13 healthy adults and cord blood of 12 healthy term newborns. Cells were subjected to differentiation toward iTregs using a transforming growth factor ß (TGF-ß)-based protocol, with or without SCFAs (acetate, butyrate, or propionate). Thereafter, they were subjected to flow cytometric phenotyping or a suppression assay. During differentiation, cells were collected for chromatin-immunoprecipitation (ChIP)-based analysis of histone acetylation. The enrichment of the TGF-ß-based protocol with butyrate or propionate potentiated the in vitro differentiation of human naïve CD4+ non-Tregs towards iTregs and augmented the suppressive capacity of the latter. These seemed to be at least partly underlain by the effects of SCFAs on the histone acetylation levels in differentiating cells. GITR, ICOS, CD39, PD-1, and PD-L1 were proven to be potential markers of human iTregs. Our results might boost the further development of Treg-based therapies against autoimmune, allergic and other chronic inflammatory disorders.

IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant ß7 integrin+ Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA+) Treg cells later in life. ß7 integrin+ Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced ß7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development.

Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early-Onset Inflammatory Bowel Disease.

BACKGROUND & AIMS: Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents. METHODS: We performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very-early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment-resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture. RESULTS: We identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-κB. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores. CONCLUSIONS: In WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD.

IL-10 Potentiates Differentiation of Human Induced Regulatory T Cells via STAT3 and Foxo1.

Foxp3(+) regulatory T cells (Tregs) play essential roles in maintaining the immune balance. Although the majority of Tregs are formed in the thymus, increasing evidence suggests that induced Tregs (iTregs) may be generated in the periphery from naive cells. However, unlike in the murine system, significant controversy exists regarding the suppressive capacity of these iTregs in humans, especially those generated in vitro in the presence of TGF-ß. Although it is well known that IL-10 is an important mediator of Treg suppression, the action of IL-10 on Tregs themselves is less well characterized. In this article, we show that the presence of IL-10, in addition to TGF-ß, leads to increased expansion of Foxp3(+) iTregs with enhanced CTLA-4 expression and suppressive capability, comparable to that of natural Tregs. This process is dependent on IL-10R-mediated STAT3 signaling, as supported by the lack of an IL-10 effect in patients with IL-10R deficiency and dominant-negative STAT3 mutation. Additionally, IL-10-induced inhibition of Akt phosphorylation and subsequent preservation of Foxo1 function are critical. These results highlight a previously unrecognized function of IL-10 in human iTreg generation, with potential therapeutic implications for the treatment of immune diseases, such as autoimmunity and allergy.

[Clinical monitoring of myocardial injury in neonates with intrauterine distress].

OBJECTIVE: To investigate whether no asphyxia neonates with intrauterine distress are complicated with myocardial injury and determine the sensitive biochemical diagnostic parameters. METHODS: A total of 89 neonates born in the First Affiliated Hospital of Sun Yat-sen University from July 2009 to December 2009 were enrolled. Fifty-three fetal distress cases with Apgar score > 7 at 1 and 5 minutes were enrolled in the study group; while the rest 36 healthy neonates, whose Apgar score = 10 at 1 and 5 minutes, were the control group. Umbilical artery blood samples of all cases were collected for blood gas analysis and biochemical measurement. RESULTS: (1) pH (7.23 ± 0.07) and BE [(-4.8 ± 3.0) mmol/L] in the study group were significantly lower than pH (7.31 ± 0.03) and BE [(-2.1 ± 1.5) mmol/L ] in the control group(P < 0.05). The lactic acid of study group [(5.2 ± 2.3) mmol/L] was higher than that of the control group [(2.3 ± 1.1) mmol/L], and the difference was significant (P < 0.01). However, there was no significant difference between the two groups in PaO2 [(16.2 ± 7.9) mm Hg (1 mm Hg = 0.133 kPa) vs. (17.5 ± 6.7) mm Hg] and PaCO2 [(54.0 ± 11.2) mm Hg vs. (48.5 ± 5.4) mm Hg; P > 0.05]. (2) The level of CK-MB in neonates with fetal distress[ (48 ± 59) U/L] was significantly higher than that of healthy neonates [(36 ± 27) U/L]. However, no significant difference was found in CK [(194 ± 73) U/L vs. (162 ± 95) U/L] and BNP levels [(519 ± 309) ng/L vs. (481 ± 216) ng/L; P > 0.05]. (3) Spearman rank correlation analysis showed that CK-MB level was negatively correlated with pH (r = -0.296, P < 0.05) and BE (r = -0.318, P < 0.05) of umbilical artery blood, while BNP level was positively correlated with umbilical lactic acid (r = 0.278, P < 0.05). No correlation was found between other parameters (P > 0.05). CONCLUSIONS: Intrauterine distress without neonatal asphyxia had effect on fetal myocardial injury. CK-MB can be used as a sensitive parameter for monitoring the development of myocardial injury. The severity of myocardial injury was related to fetal acidosis.

[Pregnant outcomes and neonatal anthropometry in women with abnormal glucose challenge test and normal oral glucose tolerance test during pregnancy.].

OBJECTIVE: To evaluate the influences of abnormal glucose challenge test(GCT) on pregnancy outcomes and neonatal anthropometric data in women with normal oral glucose tolerance test(OGTT). METHODS: Totally 214 women who delivered in the First Affiliated Hospital of Sun Yat-sen University from November 2006 to December 2007 were enrolled. 50 g GCT was performed at 24-28 weeks of gestation and 75 g OGTT would be followed if GCT >/= 7.8 mmol/L. Those patients, whose OGTT results below the following criteria (5.3 mmol/L, 10.0 mmol/L, 8.6 mmol/L, 7.8 mmol/L), were classified as normal OGTT. Altogether, 116 of the 214 women with abnormal GCT and normal OGTT were collected as the study group and the rest 98 women with normal GCT as the control group. The pregnant outcomes of the two groups were analyzed. The neonatal anthropometry, including birth weight, body length, head circumference and shoulder circumference, were recorded. Other neonatal anthropometric data, such as upper arm circumference, tricep skinfold thickness and hypodermic fat thickness of abdomen were measured by a tape measure within 24 hours after birth. RESULTS: (1) Pregnant outcomes: No significant difference was found in the rate of assisted vaginal delivery, polyhydramnios, premature rupture of membranes and fetal distress between the study and control group [10.3% (12/116) vs 4% (4/98), 5.2% (6/116) vs 10% (10/98), 13.8% (16/116) vs 17% (17/98), 20.7% (24/116) vs 13% (13/98), P > 0.05, respectively], but the rate of cesarean section, spontaneous vaginal delivery and large for gestational age babies in the study group were different from those of the control [72.4% (84/116) vs 51% (51/98), 17.2% (20/116) vs 45% (44/98), 25.9% (30/116) vs 6% (6/98), P < 0.05, respectively]. (2) Neonatal anthropometry: The birth weight of the study group was significantly higher than that of the control group [(3.4 +/- 0.4) kg vs (3.3 +/- 0.4) kg, P < 0.05], but no significant difference was shown in any other neonatal anthropometric results between the study and control group, including body length [(49.9 +/- 1.3) cm vs (49.7 +/- 1.4) cm], head circumference [(33.4 +/- 1.5) cm vs (33.8 +/- 1.7) cm], shoulder circumference [(35.4 +/- 2.3) cm vs (35.0 +/- 2.3) cm], upper arm circumference [(11.0 +/- 0.7) cm vs (10.9 +/- 0.8) cm], tricep skinfold thickness [(9.7 +/- 1.0) mm vs (9.9 +/- 1.4) mm] and hypodermic fat thickness of abdomen [(7.2 +/- 1.2) mm vs (7.2 +/- 1.0) mm; all P > 0.05]. CONCLUSION: Women with abnormal GCT alone may have no significant influences on neonatal anthropometric data, but might have more cesarean section, large for gestational age babies, and neonatal birth weight than those women with normal GCT.

Evaluation of Sodium Hypochlorite Irrigant, Bingpeng Irrigant, and Fufang Bingpeng Irrigant as Endodontic Irrigants During Passive Ultrasonic Irrigation.

Given the increasing prevalence of antibiotic resistance among bacterial strains and the side effects caused by synthetic drugs, it is increasingly important to investigate potential herbal alternatives. In the present study, antimicrobial, cell cytotoxicity, and cleaning tests were performed to evaluate the potential of Fufang Bingpeng irrigant as a root canal irrigant, in addition to q-PCR and high-throughput sequencing analyses. Our in vitro results showed a low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Fufang Bingpeng irrigant against Porphyromonas gingivalis ATCC 33277 (6.25 and 12.5%, respectively), Prevotella intermedius ATCC 25611 (6.25 and 6.25%, respectively), Fusobacterium nucleatum ATCC 25286 (6.25 and 6.25%, respectively), Enterococcus faecalis ATCC 19433 (25 and 25%, respectively), and Bacteriodes fragilis ATCC 25285 (12.5 and 12.5%, respectively). Furthermore, it effectively removed the remaining debris and increased the number of open dentinal tubules in root canals compared to the NaCl irrigant (p < 0.05). Fufang Bingpeng irrigant also presented low cytotoxicity to L929 cells compared to the NaClO irrigant. The in vivo results indicated that all irrigants used significantly reduced the number of bacteria compared to the number prior to treatment, and only 1/104.95 bacteria remained in the root canal following the use of Fufang Bingpeng irrigant (p < 0.001). Moreover, the high-throughput sequencing results indicated that all irrigants markedly enhanced the α diversity in the root canal compared to the before preparation control group, while Fufang Bingpeng maintained better microbial diversity than other groups. Therefore, Fufang Bingpeng irrigant presents a promising alternative for use as a root canal irrigant in clinical settings.

Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia.

Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.