Effect of non-pharmacological interventions on pain in preterm infants in the neonatal intensive care unit: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of different non-pharmacological interventions for pain management in preterm infants and provide high-quality clinical evidence. METHODS: Randomized controlled trials (RCTs) of various non-pharmacological interventions for pain management in preterm infants were searched from PubMed, Web of Science, Embase, and the Cochrane Library from 2000 to the present (updated March 2023). The primary outcome was pain score reported as standardized mean difference (SMD). The secondary outcomes were oxygen saturation and heart rate reported as the same form. RESULTS: Thirty five RCTs of 2134 preterm infants were included in the meta-analysis, involving 6 interventions: olfactory stimulation, combined oral sucrose and non-nutritive sucking (OS + NNS), facilitated tucking, auditory intervention, tactile relief, and mixed intervention. Based on moderate-quality evidence, OS + NNS (OR: 3.92, 95% CI: 1.72, 6.15, SUCRA score: 0.73), facilitated tucking (OR: 2.51, 95% CI: 1.15, 3.90, SUCRA score: 0.29), auditory intervention (OR: 2.48, 95% CI: 0.91, 4.10, SUCRA score: 0.27), olfactory stimulation (OR: 1.80, 95% CI: 0.51, 3.14, SUCRA score: 0.25), and mixed intervention (OR: 2.26, 95% CI: 0.10, 4.38, SUCRA score: 0.14) were all superior to the control group for pain relief. For oxygen saturation, facilitated tucking (OR: 1.94, 95% CI: 0.66, 3.35, SUCRA score: 0.64) and auditory intervention (OR: 1.04, 95% CI: 0.22, 2.04, SUCRA score: 0.36) were superior to the control. For heart rate, none of the comparisons between the various interventions were statistically significant. CONCLUSION: This study showed that there are notable variations in the effectiveness of different non-pharmacological interventions in terms of pain scores and oxygen saturation. However, there was no evidence of any improvement in heart rate.

Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns.

BACKGROUND: To explore the value of umbilical artery cord blood glucose (UACBG) in predicting hypoglycemia in gestational diabetes mellitus (GDM) and other at-risk newborns, and to provide a cut-off UACBG value for predicting hypoglycemia occurrence. METHODS: In this prospective study, we enrolled at-risk infants delivered vaginally, including neonates born to mothers with GDM, premature, macrosomic, and low birth weight. We separated the infants into GDM group and other at-risk group. All subjects underwent UACBG measurement during delivery. Neonatal peripheral blood glucose measurement was performed at 0.5 and 2 h after birth. The predictive performance of UACBG for neonatal hypoglycemia was assessed using receiver operating characteristic curve (ROC), area under curve (AUC), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: 916 newborns were included, with 538 in GDM group and 378 in other at-risk group. 85 neonates were diagnosed hypoglycemia within 2 h after birth, including 36 belonging to GDM group and 49 to other at-risk group. For hypoglycemia prediction within 2 h, the best cut-off of UACBG was 4.150 mmol/L, yielding an AUC of 0.688 (95% CI 0.625-0.751) and a NPV of 0.933. In detail, the AUC was 0.680 in GDM group (95% CI 0.589-0.771), with the optimal cut-off of 4.150 mmol/L and a NPV of 0.950. In other at-risk group, the AUC was 0.678(95% CI 0.586-0.771), the best threshold was 3.950 mmol/L and the NPV was 0.908. No significant differences were observed between GDM group and other at-risk group in AUC at 0.5 h, 2 h and within 2 h. CONCLUSIONS: UACBG has a high NPV for predicting neonatal hypoglycemia within 2 h after birth. It was implied that individuals with cord blood glucose levels above the threshold were at lower risk for hypoglycemia. UACBG monitoring provides evidence for subsequent classified management of hypoglycemia.

A Novel Cold-Adapted and High-Alkaline Alginate Lyase with Potential for Alginate Oligosaccharides Preparation.

Alginate oligosaccharides (AOs) prepared through enzymatic reaction by diverse alginate lyases under relatively controllable and moderate conditions possess versatile biological activities. But widely used commercial alginate lyases are still rather rare due to their poor properties (e.g., lower activity, worse thermostability, ion tolerance, etc.). In this work, the alginate lyase Alyw208, derived from Vibrio sp. W2, was expressed in Yarrowia lipolytica of food grade and characterized in order to obtain an enzyme with excellent properties adapted to industrial requirements. Alyw208 classified into the polysaccharide lyase (PL) 7 family showed maximum activity at 35 °C and pH 10.0, indicating its cold-adapted and high-alkaline properties. Furthermore, Alyw208 preserved over 70% of the relative activity within the range of 10-55 °C, with a broader temperature range for the activity compared to other alginate-degrading enzymes with cold adaptation. Recombinant Alyw208 was significantly activated with 1.5 M NaCl to around 2.1 times relative activity. In addition, the endolytic Alyw208 was polyG-preferred, but identified as a bifunctional alginate lyase that could degrade both polyM and polyG effectively, releasing AOs with degrees of polymerization (DPs) of 2-6 and alginate monomers as the final products (that is, DPs 1-6). Alyw208 has been suggested with favorable properties to be a potent candidate for biotechnological and industrial applications.

Effects of different doses glimepiride intake on the pharmacokinetics of benzbromarone in rats.

Benzbromarone (BNR) is prescribed for the management of hyperuricemia, whereas glimepiride (GLM) for the treatment of Type 2 Diabetes Mellitus. Both drugs are certified to be mainly metabolized via cytochrome P450 (CYP) 2C9 in vivo and may have the potential drug-drug interactions. This study aims to investigate the possible influence of orally administered low- and high-dose glimepiride (GLM) on pharmacokinetic characteristics (PK) of benzbromarone (BNR) in rats. Fifteen rats were randomly assigned to group A, B and C (n=5) and administered 0.5% sodium carboxymethyl cellulose (CMC), 0.5mg/kg GLM (low-dose) and 1.0 mg/kg GLM (high-dose) once daily for 8 days, respectively, which were all followed with a single oral dose of BNR (9.0 mg/kg) on the day 8th. Blood samples were obtained from retro orbital plexus at the time points of 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24h and BNR in plasma was quantitated by HPLC-MS/MS assay. Resultantly a slight influence of GLM on PK of BNR could be found in rats. When compared with Group A, the half-life time (t1/2z) of BNR in Group B and C significantly decreased 52.39% and 73.49%, respectively, although other major PK parameters were negligibly changed by co-administration of GLM. On the whole, the combinational therapy of GLM at low or high dose would notably alter the elimination of BNR and the effect was dose-dependent.

Effect of CD38 on B-cell function and its role in the diagnosis and treatment of B-cell-related diseases.

CD38 is a multifunctional receptor and enzyme present on the surface of B lymphocytes, which can induce B lymphocytes proliferation and apoptosis by crosslinking related cytokines to affect the function of B cells, thus affecting immune regulation in humans and promoting tumorigenesis. The level of CD38 expression in B cells has become an important factor in the clinical diagnosis, treatment, and prognosis of malignant tumors and other related diseases. Therefore, studying the relationship between CD38 expression on the surface of B cells and the occurrence of the disease is of great significance for elucidating its association with disease pathogenesis and the clinical targeted therapy. In this paper, we review the effects of CD38 on B-cell activation, proliferation, and differentiation, and elaborate the functional role and mechanism of CD38 expression on B cells. We also summarize the relationship between the level of CD38 expression on the surface of B cells and the diagnosis, treatment, and prognosis of various diseases, as well as the potential use of targeted CD38 treatment for related diseases. This will provide an important theoretical basis for the scientific research and clinical diagnosis and treatment of B-cell-related diseases.

The role of Tim-3/Galectin-9 pathway in T-cell function and prognosis of patients with human papilloma virus-associated cervical carcinoma.

The interaction between Tim-3 on T cell and its ligand, Galectin-9, negatively regulates cellular immune responses. However, the role of Tim-3/Galectin-9 pathway in the immune evasion of cervical cancer remains unknown. This study is to investigate the expression, function, and regulation of Tim-3/Galectin-9 signaling pathway in human papilloma virus (HPV) positive cervical cancer. Flow cytometry showed that Tim-3 expression on T cell and Galectin-9 expression on monocytes in HPV positive cervical cancer patients were significantly higher compared to cervical intraepithelial neoplasia and benign uterine fibroids Tim-3 + CD4+ Th1 cells and Tim-3 + CD8+ T cells in HPV positive cervical cancer patients were significantly reduced after surgery. Serum TGF-ß and IL-10 levels were positively correlated with Tim-3 + Treg cells, while IFN-γ and IL-2 were negatively correlated with Tim-3 + Th1 cells. Additionally, Tim-3 + CD4+ T cells were positively correlated with Galectin-9 + monocytes. Survival curve analysis showed that Tim-3 + CD4+ T cells were negatively correlated with patient survival, and closely related to FIGO stage, degree of differentiation, and lymph node metastasis of HPV positive cervical cancer. In vitro experiments showed that by blocking the Tim-3/Galectin-9 pathway, the proliferation of T cells and their ability to express IFN-γ, IL-2, perforin, and granzyme B was significantly restored. In conclusion, high levels of Tim-3 and Galectin-9 in HPV positive cervical cancer patients play roles in the progression of disease by promoting Treg cells to inhibit the cytotoxic function of Th1 and CD8+ T cells. Tim-3/Galectin-9 may serve as a new immunotherapy target for patients with HPV positive cervical cancer.

Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2.

Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.

Gestational hypertensive disease and small for gestational age infants in twin pregnancy: A systematic review and meta-analysis.

AIM: The review is to explore the connection between gestational hypertension diseases (GHD) and small for gestational age (SGA) in twin pregnancies. METHODS: According to the recommendations of PRISMA, relevant studies were systematically searched through PubMed, Web of Science, Cochrane Library, Embase from inception until January 16, 2022. Subgroup analysis was performed according to chorionicity and diagnostic criteria of SGA. Odds ratios (OR) were assessed to judge the link between GHD and SGA in twin pregnant women. A random-effect model was used to estimate the pooled hazard ratio when there was significant heterogeneity (I2  > 50%); otherwise, a fixed-effect model was conducted. RESULTS: Seven articles containing 470 589 twin pregnant women were included. The increased risk of SGA was connected to the twin pregnancies complicated with GHD (OR = 1.57, 95% confidence interval [CI] = 1.10-2.24, p = 0.01). After subgroup analysis, the connection between SGA and GHD had no statistical significance (OR = 1.17, 95% CI = 0.95-1.44, p = 0.14) when the enrolled studies using the SGA diagnosis referred to singleton birth weight, but significant (OR = 2.14, 95% CI = 1.77-2.60, p<0.001) in the group using the SGA diagnosis referred to twin birth weight. Stratified by chorionicity, SGA was relevant to GHD in the dichorionic (DC) group (OR = 1.68, 95% CI = 1.17-2.42, p = 0.005), while not in the monochorionic (MC) group (OR = 1.68, 95% CI = 0.93-3.03, p = 0.09). More future articles are warranted to confirm these outcomes. CONCLUSIONS: Our review demonstrated that GHD in DC twin pregnancies was related to an enlarged risk of SGA. Two SGA diagnosis references led to different results. Twin pregnancies complicated with GHD were at significantly higher risk of SGA when twin birth weight reference was used.

Merging Imidazolidines with a Trifluoromethylated Tetrasubstituted Carbon through Tungsten Catalyzed 1,3-Dipolar Cycloaddition.

An unprecedented 1,3-dipole cycloaddition between acyclic CF3-ketimines and N-benzyl azomethine ylide has been allowed by tungsten catalysis, furnishing a range of novel imidazolidines bearing a trifluoromethylated tetrasubstituted carbon center. This reaction appears as one of rare examples that challenging acyclic CF3-ketimines have been engaged in 1,3-cycloaddition reactions. The capability for gram-scale synthesis and variant derivatizations of cycloaddition adducts illustrates the synthetic potential of this approach. This protocol provides a facile access to a rapidly enlarging pool of motifs with a trifluoromethylated fully substituted carbon.

Dynamic changes of coagulation and fibrinolytic biomarkers in peri operaive arthroplasty patients.

OBJECTIVE: To evaluate coagulation and fibrinolytic parameters after total joint arthroplasty (TJA) and provide evidence for optimization of timing of perioperative anticoagulation medicine. METHODS: The prospective study was conducted at the Jishuitan Hospital of Peking University from January to April in 2016, and comprised patients who were scheduled consecutively to undergo primary total knee arthroplasty (TKA) or total hip arthroplasty (THA). Blood samples were obtained at day 1 preoperatively and day1, day 3 postoperatively. Antigenic levels of protein C (PC), endothelial protein C receptor (EPCR), tissue factor pathway inhibitor (TFPI), antithrombin III (AT-III), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) were measured with commercially available enzyme-linked immunosorbent assay kits. RESULTS: Postoperative levels of coagulation parameters TFPI and AT-III were increased compared to preoperative values (118.7±34.6 vs 70.0±20.5 µg/ml for AT-III, and 26.37±7.91vs 16.68±8.92 µg/l for TFPI), while postoperative levels of coagulation parameters PC and EPCR were decreased (0.88±0.30 vs 2.03±0.66 µg/ml for PC, and 100.8±31.0 vs 199.4±57.4 µg/ml for EPCR). Postoperative levels of fibrinolytic parameter tPA was increased compared to preoperative values (2.87±0.83 vs 2.03±1.03 µg/l), while its specific inhibitor PAI-1 was decreased (0.88±0.30 vs 2.03±0.66 µg/l). CONCLUSIONS: These results demonstrated the perturbation of the coagulation and fibrinolytic system of patients undergoing TJA. Hypercoagulation and hyperfibrinolysis were observed in postoperative patients, which suggested anticoagulant therapy is effective and necessary.

Effect of inappropriate admissions on hospitalization performance in county hospitals: a cross-sectional study in rural China.

BACKGROUND: Inappropriate admissions cause excessive utilization of health services compared with outpatient services. However, it is still unclear whether inappropriate admissions cause excessive use of health services compared with appropriate admissions. This study aims to clarify the differences in the hospitalization performances between appropriately admitted inpatients and inappropriately admitted inpatients. METHODS: A total of 2575 medical records were obtained after cluster sampling in three counties. Admission appropriateness was assessed by appropriateness evaluation protocol (AEP). The propensity score matching (PSM) was computed to match patients in treatment and control group with similar characteristics, and to examine the differences in the utilization of hospitalization services between the two groups. The samples were matched in two major steps in this study. In the first step, total samples were matched to examine the differences in the utilization of hospital services between the two groups using 15 individual covariates. In the second step, PSM was computed to analyze the differences between the two groups in different disease systems using 14 individual covariates. RESULTS: For the whole sample, the inappropriate group has lower expenditure of hospitalization (EOH) (difference = - 0.12, p = 0.003) and shorter length of stay (LOS) (difference = - 0.73, p = 0.016) than the appropriate group. For number of clinical inspection (NCI), it has no statistically significant difference (difference = - 0.39, p = 0.082) between the two groups. Among different disease systems, no significant differences were observed between the two groups among EOH, LOS and NCI, except that the EOH was lower in the inappropriate group than that in the appropriate group for surgical disease (difference = - 0.169, p = 0.043). CONCLUSION: Inappropriate admissions have generated excessive health service utilization compared with appropriate admissions, especially for internal diseases. The departments in charge of medical services and hospital managers should pay high attention to the health service utilization of the inappropriately admitted inpatients. Relevant medical policies should be designed or optimized to increase the appropriateness in health care service delivery and precision in clinical pathway management.

Role of Regulatory B Cells in the Progression of Cervical Cancer.

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P < 0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P < 0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r = 0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P < 0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r = -0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P < 0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

Epidemiology and Risk Factors of Menopause Syndrome Among Uyghur, Han, and Kazak Women in Xinjiang, China.

BACKGROUND This study analyzed the epidemiology and the risk factors of menopause syndrome (MPS) among Uyghur, Han, and Kazak women in Xinjiang. MATERIAL AND METHODS This was a cross-sectional study. The stratified-cluster random-sampling method was used. A total of 3382 women aged 40 to 60 years of age were included from Urumqi City, Kashgar City, Altay City, Ili Kazakh Autonomous Prefecture, Künes County, Mongolkure County, Tekes County,Talede town, Alemale Township, and Ulugchat County (Kashgar Prefecture) in Xinjiang Province. A questionnaire was used to survey the clinical characteristics of MPS. Logistic regression analysis was used to analyze the MPS risk factors among Uyghur, Han, and Kazak women. RESULTS Oral contraceptives, negative life events, and menopause stages can influence MPS in Han women. In addition, occupation, body weight, mental illness, drug or alcohol abuse, and income level also affect the MPS of Uyghur women. In contrast to Han and Uyghur participants, education, menopausal pattern (natural or artificial), reproductive factors, and smoking are risk factors of MPS in Kazakh women. CONCLUSIONS The menopausal stages and the risk factors for MPS are different among Uyghur, Han, and Kazak women.

CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions.

Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed. CCK8 assay and colony formation assay indicated that CD38 promoted cervical cancer cell proliferation. Nude mouse tumorigenicity assay showed that CD38 significantly promotes tumor growth in vivo. CD38 also induced S phase accumulation in cell cycle analysis and suppressed cell apoptosis in cervical cancer cells. Meanwhile, flow cytometry analysis of mitochondria functions suggested that CD38 decreased intracellular Ca2+ levels in cervical cancer cells and CD38 was involved in down-regulation of ROS levels and prevented mitochondrial apoptosis in cervical cancer cells. The percentage of cells with loss of mitochondrial membrane potential (Δψm) in CD38-overexpressed cervical cancer cells was less than control groups. Furthermore, we found an up-regulation of MDM2, cyclinA1, CDK4, cyclinD1, NF-kB P65, c-rel, and a downregulation of P53, P21, and P38 by Western blot analysis. These results indicated that CD38 enhanced the proliferation and inhibited the apoptosis of cervical cancer cells by affecting the mitochondria functions.

Fluorescence array-based sensing of nitroaromatics using conjugated polyelectrolytes.

A sensor array consisting of six cationic fluorescent conjugated polyelectrolytes (CPEs) is reported, which could readily differentiate between nine closely related hydrophilic nitroaromatics (NACs) in separate aqueous solutions by fluorescence pattern recognition and linear discrimination analysis (LDA).

Elevated Expression of Programmed Death-1 and Programmed Death Ligand-1 Negatively Regulates Immune Response against Cervical Cancer Cells.

The present study is to measure the expression of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), as well as its clinical significance in cervical cancer patients. Our results showed that different T cell subsets in patients with cervical cancer had high expression of PD-1, and DCs had high expression of PD-L1. High expression of PD-1 on Treg cells in cervical cancer patients facilitated the production of TGF-ß and IL-10 but inhibited the production of IFN-γ. Cervical cancer elevated the expression of PD-1 and PD-L1 in mRNA level. PD-1 expression in peripheral blood of cervical cancer patients was related with tumor differentiation, lymph node metastasis, and invasiveness. PD-1/PD-L1 pathway inhibited lymphocyte proliferation but enhanced the secretion of IL-10 and TGF-ß in vitro. In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-ß, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer. Therefore, PD-1/PD-L1 pathway may become an immunotherapy target in the future.

Physical activity trajectory during pregnancy and associations with maternal fatigue using a growth mixture modeling approach.

The purpose of this study was to investigate the associations of physical activity trajectories with maternal fatigue. Pregnant women provided objectively assessed physical activity data by Pregnancy Physical Activity Questionnaire four times. Fatigue scale-14 was used to assess fatigue during pregnancy. Growth mixture modelling characterized physical activity trajectories across pregnancy. The generalized estimating equations was used to analyze the relationship between different physical activity profiles and fatigue in pregnant women. A total of 626 pregnant women were included in analysis in a teaching hospital in Nantong city. Fatigue (total, mental and physical) was not different between two groups based on total energy expenditure of PA (constantly high vs. constantly low). The pregnant women in "constantly high household PA" group had the higher fatigue compared to "constantly low household PA" (P < 0.05) and "constantly medium household PA" (P < 0.05). The pregnant women in "constantly high sport PA" group had lower fatigue compared to "constantly low sport PA" (P < 0.05). Household PA and sport PA were still an independent influencing factor for fatigue after controlling for confounding variables. Specifically, we observed that higher household PA and lower sport PA were associated with higher fatigue during pregnancy.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

Human ß-defensin messenger RNA is overexpressed in the cervical epithelia of patients with nongonococcal cervicitis.

OBJECTIVE: Human ß-defensin (hBD) is an innate immune mediator present in the mucosae. This study aimed to investigate whether hBD is implicated in nongonococcal cervicitis (NGC). MATERIALS AND METHODS: Seventy-two patients with NGC and 64 healthy volunteers were consecutively enrolled between April 2010 and May 2011. Sensitive antimicrobial treatment was assigned to patients with NGC. Cervical tissues were sampled for the semiquantitative reverse transcription-polymerase chain reaction analyses of hBD-1, hBD-2, and hBD-3 messenger RNA (mRNA) expression. RESULTS: The hBD-1, hBD-2, and hBD-3 mRNAs were comparably expressed in normal cervical tissues. The expression of hBD-1 mRNA was similar between patients with NGC and control subjects, whereas those of hBD-2 and hBD-3 mRNAs were significantly up-regulated in patients with NGC (1.25 [0.38] vs 1.08 [0.31], p = .005; 1.26 [0.35] vs 1.04 [0.30], p < .001). The relative expression level of hBD-1 mRNA remained unchanged in pathogen-eliminated patients, whereas those of hBD-2 mRNA (1.33 [0.42] vs 1.04 [0.36], p = .012) and hBD-3 mRNA (1.23 [0.32] vs 1.13 [0.26], p = .009) decreased significantly after the successful antimicrobial treatment. CONCLUSIONS: Expressions of hBD-2 and hBD-3 mRNA are up-regulated in NGC, suggesting the role of mucosal immunity in NGC.

EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1.

Objective: This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism. Methods: Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1ß, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified. Results: OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation. Conclusion: Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.