Involvement of regulation of the excitation:inhibition functional balance in the mPFC in the antidepressant-anxiolytic effect of YL-IPA08, a novel TSPO ligand.

TSPO, an 18 kDa translocator protein, has received increased attention due to its antidepressant-anxiolytic effects. The balance between glutamatergic and GABAergic (E: I) in the medial prefrontal cortex (mPFC) is crucial for antidepressant-anxiolytic effects. However, no evidence is available to clarify the relationship between TSPO and E:I balance. In the present study, we used the TSPO global-knockout (KO) and TSPO wild-type (WT) mice to assess the effects of TSPO on antidepressant-anxiolytic effects of YL-IPA08 (a novel TSPO ligand) and the underlying neurobiological mechanism. Additionally, a multichannel electrophysiological technique was used to explore the effects of YL-IPA08 on pyramidal neurons and interneurons in mPFC. Open field test (OFT) and elevated plus maze (EPM) test revealed that a single dose of YL-IPA08 (0.3 mg/kg, i.p.) exhibited significant anxiolytic actions in WT mice except in KO mice. In only WT mice, significant antidepressant effects were observed in tail suspension test (TST) and forced swim test (FST). The multichannel electrophysiological technique demonstrated that YL-IPA08 significantly increased the firing rates of pyramidal neurons and decreased those of interneurons. Further studies illustrated that the firing rates of glutamatergic might be antagonized by PK11195 (a classic TSPO antagonist). Our results suggest that YL-IPA08 might regulate the E:I balance in mPFC, mediated by TSPO. In summary, TSPO regulates E:I functional balance in mPFC, play a critical role in antidepressant-anxiolytic effects of YL-IPA08, and provide a potential target site for the development of antidepressant and anxiolytic drugs.

Progress on genic male sterility gene in soybean.

Male sterility refers to the phenomenon that stamens cannot grow normally and produce viable pollen grains in plants. Hybrid seed production by taking advantage of the trait of male sterility is an effective and quick strategy to increase crop yield. Up to date, the yield of rice (Oryza sativa L.), maize (Zea mays L.), wheat (Triticum aestivum L.) and other crops has been greatly increased based on hybrid vigor utilization. Soybean (Glycine max (L.) Merr.) is a self-pollination species, artificial emasculation is not only time-consuming, but also labor-intensive and economically impracticable. So far, large scale hybrid breeding has not been performed in soybean due to the shortage of male sterile lines suitable for hybrid production. Therefore, it is urgent to identify a stable male sterile system for the rapid utilization of heterosis in soybean. In this review, we summarize the progress on the discovery of soybean genic male sterility (GMS) mutants and GMS genes. Combining with the investigation of GMS genes in Arabidopsis, rice and maize, we provide important insights into the identification and potential utilization of GMS genes in soybean in the perspective of reverse genetics.

Brain Abnormalities in Different Phases of Working Memory in Schizophrenia: An Integrative Multi-Modal MRI Study.

The current study aimed to examine both gray matter and functional activity changes in schizophrenia by combing both structural and task-related functional magnetic resonance imaging (fMRI). Nineteen patients with schizophrenia and 17 controls were recruited. The fMRI scan was performed while performing a working memory (WM) task. In terms of task performance, accuracy did not differ between groups, but there were significant differences in reaction time. Compared with controls, patients exhibited decreased functional activation in prefrontal areas, insula, lingual gyrus, and superior temporal gyrus during different phases of WM. The subcallosal cortex showed increased activation. Intriguingly, a structural-functional correlation was found in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and subcallosal cortex in patients when performing high-load WM task. This study demonstrated both impaired gray matter volume and functional activation during WM in schizophrenia, suggesting structural and functional impairments. The structural-functional correlation in schizophrenia suggested that structural damage in schizophrenia might induce a decreased ability to modulate functional response in accordance with increasing task difficulty.

Allergy in patients with anti-N-methyl-d-aspartate receptor encephalitis.

BACKGROUND AND OBJECTIVE: Allergy is a potential outcome of dysregulated immune system. Previous studies have shown the association of allergy and autoimmune diseases, however, there is few study to investigate the relationship between allergy and anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Thus, we investigate the rate of allergy in patients with anti-NMDAR encephalitis and analyze the risk factors. METHOD: The rate of allergy was investigated in patients with anti-NMDAR encephalitis and was compared with patients with virus encephalitis. The clinical cutaneous characters were described in details. All patients with anti-NMDAR encephalitis were divided into allergic and nonallergic group. Clinical factors were compared in the two groups, and logistic regression model was also used to analyze possible risk factors of allergy. RESULTS: Patients with anti-NMDAR encephalitis had a higher rate of allergy than those with viral encephalitis (22.1% vs 9.2%, odds ratio (OR)=3.23, confidence interval (CI)=1.40-7.42, P=0.006). In patients with anti-NMDAR encephalitis, allergic patients exhibited longer days in hospital (30days vs 22days, P=0.005) and higher occurrence of decreased consciousness (81.5% vs 58.9%, P=0.031), higher rate of complications (77.8% vs 57.9%, P=0.046) and abnormal electroencephalography (EEG) (100% vs 78.6%, P=0.021) than patients without allergy. Cerebrospinal fluid (CSF) antibody titers of allergic patients during the disease course were also higher than nonallergic patients (P=0.004). However, further logistic regression analysis did not reveal independent predictors of allergy. CONCLUSIONS: Patients with anti-NMDAR encephalitis show higher allergic rate than those with virus encephalitis. Patients with allergy show higher CSF antibody titers and greater illness severity. However, the final outcome of anti-NMDAR encephalitis was not influenced.

Late-onset anti-N-methyl-d-aspartate receptor encephalitis in China.

PURPOSE: This study aimed to summarize the clinical characteristics and outcome of late-onset anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis in China. METHOD: All cases of people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and April 2017 were retrospectively reviewed. The demographics, clinical characteristics, and outcome of those patients (age≥45years old) were summarized. Comparisons were conducted between older (≥45years old) and younger (18-44years old) adults. RESULT: Eighteen (12%) of 151 people were ≥45years old, 9 of whom (50%) were female. Psychiatric symptoms were the most common clinical manifestations of older adults and presented in all individuals. At the last follow-up, 14 (78%) of them had a good outcome (modified Rankin Scale: 0-2) and one (6%) died. Compared with 121 younger adults, older adults had a higher proportion of presenting memory deficit as the initial symptom (17% vs. 2%, p=0.023), longer interval from onset to admission (30 vs. 13days, p=0.013), and longer interval from onset to diagnosis (42.5 vs. 24days, p=0.045). No older adults' condition was accompanied with teratoma compared with 75% of younger adults with tumor (p=0.032). And older adults had a tendency to have a lower rate of positive NMDAR antibody (Ab) in serum (28% vs. 52%, p=0.053). CONCLUSION: Delayed admission and diagnosis are more common in older adults than in younger adults. A comprehensive consideration of all symptoms and early screening of NMDAR Ab, especially in cerebrospinal fluid, is necessary and beneficial to differential diagnosis.

Effects of emergency cervical cerclage on pregnancy outcome: a retrospective study of 158 cases.

The aim of this study was to evaluate the effectiveness and safety of emergency cervical cerclage in women with advanced cervical dilatation and bulging of fetal membranes. The study included 158 women who underwent emergency cervical cerclage because of cervix dilatation and protruding membranes in mid-trimester at Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Pregnancy outcomes and pregnancy outcome related to clinical features were analyzed retrospectively. Analysis revealed that the placement of emergency cerclage led to the delivery of live infants with a success rate of 82.28%. The mean interval between cerclage and delivery was 52.16.±26.62 days, with a mean gestation at delivery of 30.3±4.7 weeks and a mean birth weight of 1934.69±570.37 g. No severe maternal complications such as maternal death, hematosepsis, and hysterorrhexis occurred after the operation. Two women (1.25%) had laceration of the cervix, 1 woman (0.61%) suffered pulmonary edema, and 2 women (1.25%) developed deep vein thrombosis (DVT). There were significant correlations between the pregnancy outcome and risk factors, including any presenting symptoms, cervical dilatation, postoperative white blood cell count, and C-reactive protein (CRP) value. No significant difference was found in women with good vs. poor outcome in terms of maternal age and obstetric histories. Emergency cervical cerclage is effective in prolonging pregnancy and improving neonatal outcome in women with cervical incompetence. It should be considered a viable option for women with a dilated cervix in mid-trimester.

Effect of melilotus extract on lung injury by upregulating the expression of cannabinoid CB2 receptors in septic rats.

BACKGROUND: M. Suaveolens Ledeb has long been used in China to treat inflammatory infectious diseases. Melilotus is extracted from Melilotus Suaveolens Ledeb and its therapeutic potential is associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of melilotus extract in a rat cecal ligation and puncture (CLP)-induced animal model of acute lung injury (ALI). METHODS: A sepsis model was induced by CLP-like lung inflammation. Two hours prior to CLP administration, the treatment group was administered melilotus extract via oral injection. RT-PCR and Western blotting were used to test the expression of cannabinoid receptor (CB)2, NF-κß and IκB from single peripheral blood mononuclear cells and lung tissues respectively. Enzyme linked immune sorbent assay was used to detect serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and IL-12. The numbers of neutrophils, lymphocytes, macrophages and total cells in the bronchoalveolar lavage (BAL) fluid were counted. For histologic analysis, hematoxylin and eosin (H&E) stains were evaluated. RESULTS: After inducing ALI by CLP for 24 hours, melilotus extract up-regulated peripheral blood mononuclear cell CB2 expression, blocked the activity of NF-κß65, and the number of neutrophils, lymphocytes and total cells were significantly lower in the melilotus extract group than the control group. In addition, TNF-α and IL-6 levels were significantly decreased in the melilotus extract group. Histological results demonstrated the attenuation effect of melilotus extract on CLP-induced lung inflammation. CB2 was negatively correlated to NF-κß mRNA and proteins, respectively (r = -0.377, P < 0.05; r = -0.441, P < 0.05). CONCLUSION: The results of this study indicated melilotus extract significantly reduced CLP-induced lung inflammation by up-regulating CB2 expression. The remarkable protective effects of melilotus extract suggest its therapeutic potential in CLP induced-acute lung injury treatment.

[Retracted] miR­639 is associated with advanced cancer stages and promotes proliferation and migration of nasopharyngeal carcinoma.

[This retracts the article DOI: 10.3892/ol.2018.9512.].

Changes of insulin resistance and ß-cell function in women with gestational diabetes mellitus and normal pregnant women during mid- and late pregnant period: a case-control study.

AIM: The aim of this study was to observe insulin resistance and ß-cell function changes among women diagnosed with gestational impaired glucose tolerance or gestational diabetes mellitus (GDM) in mid-pregnancy. MATERIAL AND METHODS: Sixty-four pregnant women receiving prenatal care underwent an oral glucose tolerance test at 20-24 weeks of gestation and an insulin release test. The GDM group included 34 pregnant women diagnosed with gestational impaired glucose tolerance or GDM, and the subjects with normal blood glucose were the control group. Insulin resistance and islet ß-cell function changes were observed with the oral glucose tolerance test and insulin release test. RESULTS: The homeostatic model assessment-ß levels in late pregnancy were higher than those in mid-pregnancy for both groups, and the primary time effect was statistically significant. The early insulin secretion index (ΔI(30)/ΔG(30)) values in mid- and late pregnancy were lower in the GDM group. The values of the area under the curve of blood glucose in mid- and late pregnancy were higher in the GDM group than those in the control group. Insulin resistance was higher in GDM patients than in normal pregnant women. CONCLUSIONS: Insulin resistance was aggravated, and ß-cell's ability to compensate for the increased insulin resistance by modulating insulin secretion was aggravated, as gestational week increased in women with gestational diabetes and normal pregnant women. Insulin resistance in women with GDM is higher than in pregnant women with normal metabolism of glucose.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Characteristics of Facial Muscle Activity Intensity in Patients With Schizophrenia and Its Relationship to Negative Symptoms.

Introduction: Previous studies have shown that in addition to having impairments in facial emotion recognition, patients with schizophrenia also show a lack of facial expression. Although negative symptoms such as decreased facial activity are common symptoms of schizophrenia, the related factors remain inconclusive. Therefore, this study compared healthy controls to explore the characteristics of facial muscle activity intensity in patients with schizophrenia and its relationship with negative symptoms. Methods: This observational and cross-sectional study conducted in a psychiatric hospital in China included a total of 135 patients with schizophrenia and 134 healthy controls. The negative symptoms of schizophrenia were evaluated using the Brief Negative Symptom Scale. The intensity of facial muscle activity under positive, neutral, and negative emotional stimuli conditions was automatically collected by a computer, including 17 values (F01-F17) that represent different facial muscle activities. Statistical tests were performed to analyze facial muscle activity indexes, to explore an objective and quantitative method to evaluate the negative symptoms of schizophrenia. Results: The facial muscle activity intensity of the schizophrenia group at F02 (outer eyebrow), F04 (upper eyelid), F07 (nose), F10 (dimple), F12 (lower jaw 1), F14 (lip 2), and F17 (blink) was lower than that of the healthy controls (p < 0.05). Under positive, neutral, and negative emotional stimuli conditions, the facial muscle activity intensity of F16 (lower jaw 2) was positively correlated with negative symptoms (p < 0.05). Conclusion: Our study indicated that patients with schizophrenia show defects in facial muscle activity and that is associated with negative symptoms.

The role of the excitation:inhibition functional balance in the mPFC in the onset of antidepressants.

Currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), generally require weeks to months to produce a therapeutic response, but the mechanism of action underlying the delayed onset of antidepressant-like action remains to be elucidated. The balance between excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons, i.e., the excitation:inhibition functional (E:I) balance, in the medial prefrontal cortex (mPFC) is critical in regulating several behaviors and might play an important mediating role in the mechanism of rapid antidepressant-like action reported by several studies. In the present study, the multichannel electrophysiological technique was used to record the firing activities of pyramidal neurons and interneurons and investigate the effects of a single dose of fluoxetine and ketamine (both 10 mg/kg, i.p.) on the E:I functional balance in the rat mPFC after 90 min or 24 h, and the forced swimming test (FST) was used to evaluate the antidepressant-like effects of fluoxetine and ketamine. The present study also explored the effects of chronic treatment with fluoxetine (10 mg/kg, i.g.) for 7 d or 21 d on the E:I functional balance in the mPFC. The present results suggested that a single dose of ketamine could both significantly increase the firing activities of pyramidal neurons and significantly decrease the firing activities of interneurons in the mPFC and exerted significant antidepressant-like action on the FST after 90 min and 24 h, but fluoxetine had no such effects under the same conditions. However, chronic treatment with fluoxetine for 21 d (but not 7 d) could significantly affect the firing activities of pyramidal neurons and interneurons in the mPFC. Taken together, the present results indicated that rapid regulation of the E:I functional balance in the mPFC might be an important common mechanism of rapid-acting antidepressants and the delayed onset of SSRIs might be partly attributed to their inability to rapidly regulate the E:I functional balance in the mPFC. The present study provided a new entry point to the development of rapid-acting antidepressants.

Deficits of Tactile Passive Perception Acuity in Patients With Schizophrenia.

Background: Scarce literature has yet to characterize the tactile discrimination capability as well as the underlying mechanism of tactile deficits in psychotic disorder. In particular, very little is known regarding the tactile perception acuity in schizophrenia. Methods: A total of 131 clinically stable patients with schizophrenia (SCZ) and 79 healthy control (HC) volunteers were enrolled in the study. All the participants were tested on a tactile stimulus device which could quantify the tactile discrimination capability with right index finger scanned over the angles via the passive finger-movement apparatus. The MATRICS Consensus Cognitive Battery (MCCB) was adapted to assess the neurocognition of the participants. Correlation analysis and multivariate linear regression analysis were performed to investigate the relationship between tactile perception performance and neurocognitive function. Results: It was discovered that there existed a significant deficits in the tactile passive perception acuity (i.e., tactile angle discrimination threshold) in patients with schizophrenia compared with their healthy controls (F (3, 206) = 11.458, P = 0.001,partial η2 = 0.053). The MCCB total score and its six domains were significantly lower in SCZ patients than those in HCs (all p < 0.001). In the SCZ group, the composite score of the MCCB (r = -0.312, P < 0.001) and domains of neurocognition including speed of processing (r = -0.191, P = 0.031), attention/vigilance (r = -0.177, P = 0.047), working memory (r = -0.316, P < 0.001), verbal learning (r = - 0.332, P < 0.001), visual learning (r = -0.260, P = 0.004), and reasoning and problem solving (r = -0.209, P = 0.018) showed significant negative correlations with the tactile angle discrimination threshold. Multivariate linear regression analysis revealed that neurocognition impairment, especially the decline of working memory (B = -0.312, P < 0.001),underpin the tactile perception discrimination deficits in patients with SCZ. Conclusion: To the best of our knowledge, this is the first study to unravel the deficits of tactile passive perception acuity and its underlying neurocognition basis in patients with SCZ. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder.

[Clinical experience of using oxytocin antagonist atosiban in the rescue therapy of preterm labour].

OBJECTIVE: To investigate the effectiveness of oxytocin antagonist atosiban in the alternative rescue therapy of preterm labor. METHODS: Alternative tocolysis atosiban was given as rescue therapy to 35 women, who had received ritodrine or magnesium sulphate but failed, due to either progression of labour or intolerable adverse events. Atosiban was administered for up to 48 hours. Efficacy and tolerability were assessed based on the proportion of women who did not deliver and did not need alternative tocolytic therapy at 48 hours and 7 days after therapy initiation. The numbers of maternal adverse events and neonatal morbidity were also assessed. RESULTS: Efficacy and tolerability at 48 hours and 7 days after atosiban initiation were 77% (27/35) and 60% (21/35). One woman presented drug-related side effects with mild nausea and vomiting. Thirty-four women have delivered and one bigemina (28 weeks) is being followed-up. In 34 women, 11 delivered before 28 gestational weeks, 17 delivered after 28 gestational weeks, 3 delivered after 34 weeks and 3 had term delivery. Pregnancies were prolonged by 4 hours to 14(+2) weeks. There were nine neonatal deaths, with gestational ages less than 28 weeks at delivery. CONCLUSION: Oxytocin antagonist atosiban could be given as alternative rescue therapy if therapy with ritodrine or magnesium sulphate fails in the treatment of preterm labor, and it is safe and effective.

miR-639 is associated with advanced cancer stages and promotes proliferation and migration of nasopharyngeal carcinoma.

Early detection of nasopharyngeal carcinoma (NPC) is of vital importance for improving prognosis and survival rates. MicroRNA (miRNA) are a class of short and non-coding RNA molecules that are capable of inhibiting the translation of mRNA of target genes. Previous studies have revealed that miRNA are involved in tumorigenesis and cancer development. The RNase-resistance of circulating miRNA have made them valuable non-invasive biomarkers, and has therefore drawn particular attention to their therapeutic potential. The aim of the present study was to investigate the expression of the previously uncharacterized miR-639 in NPC. In a study population of 139 patients, higher expression of miR-639 was associated with metastasis, more advanced cancer stages, and lower disease-free survival rates. In vitro experiments involving transfection of human NPC C666-1 and NPC/HK1 cell lines with miR-639 mimics and antagomir indicated that overexpressing miR-639 promoted cell proliferation and migration, suppression of miR-639 inhibited proliferation and migration. The present study provides evidence that miR-639 is differentially expressed in NPC tissues of varying cancer stages, and suggests that quantifying circulating miR-639 may be of importance for non-invasive diagnosis and prognostic evaluation, and may have potential therapeutic utility.

[Influential factors of systemic lupus erythematosus activity during pregnancy and its relationship with pregnancy outcome].

OBJECTIVE: To investigate the influential factors of systemic lupus erythematosus (SLE) activity during pregnancy and their relationship with pregnancy outcome. METHODS: A retrospective analysis of the clinical history of 66 pregnant women with SLE from 1991 to 2005 was carried out. RESULTS: (1) Those patients with unstable status progestation, patients being newly diagnosed with SLE during pregnancy or patients irregularly using prednisone became active during pregnancy. The disease was active in 32 cases (the active group) and inactive in 34 cases (the inactive group). (2) Obstetric complications in the active group included: 9 cases of preeclampsia, 13 cases of fetal growth restriction (FGR), 7 cases of therapeutic abortion and 15 cases of premature labor; and the corresponding numbers in the inactive group were 1, 5, 1 and 4, respectively. All the numbers were significantly different between the two groups (P < 0.05). (3) Among all SLE injuries, the lupus nephropathy affected pregnancy mostly. With the logistic regression advanced method, we found the lupus nephropathy was the independent risk factor for preeclampsia and FGR. (4) The rates of preeclampsia, and fetal losses were 4.7% (2/43) and 9.3% (4/43) in the patients taking prednisone less than 15 mg/day, and were 33.3% (6/18) and 44.4% (8/18) in the patients taking prednisone more than 20 mg/day, being significantly different from the former (P < 0.01). CONCLUSIONS: Being unstable progestation, being newly diagnosed during pregnancy or irregular prednisone use are important influential factors of SLE activity. SLE flares during pregnancy, especially the lupus nephropathy correlate closely with the adverse pregnancy outcomes. The rates of preeclampsia, and fetal losses increase in the patients taking prednisone more than 20 mg/day compared with the patients taking prednisone less than 15 mg/day.

[Placental expression of human histocompatibility antigen-G mRNA in idiopathic fetal growth restriction and its relationship with pathological changes of placenta].

OBJECTIVE: To investigate the expressions of human histocompatibility antigen-G (HLA-G) mRNA in placenta of idiopathic fetal growth restriction (IFGR) and its relationship with pathogenesis of IFGR. METHODS: In situ hybridization was used to investigate the expression level and distribution of HLA-G mRNA in placentas of 20 cases of idiopathic IFGR and 28 cases of control group. HE stain was applied to observe the pathological changes of the placenta. RESULTS: (1) The incidence of placental pathological lesions in idiopathic IFGR (75%) was notably higher than those of the control group (18%), (chi2 = 15.67, P = 0.001). (2) In situ hybridization showed the positive expression rate of HLA-G mRNA in placenta of idiopathic IFGR was 45%, that of control group was 79%, with significant difference between the two groups (chi2 = 5.75, P = 0.017). HLA-G mRNA signal mainly expressed in cytotrophoblast and syncytiotrophoblast. (3) There was negative correlation between the expression rate of HLA-G mRNA and incidence of placental pathological lesions (r = -0.638, P = 0.008). CONCLUSIONS: There is a significant decrease in the expression of HLA-G mRNA in IFGR. HLA-G may play a role in the pathogenesis of IFGR.

Effect of Melilotus extract on lung injury via the upregulation of tumor necrosis factor-α-induced protein-8-like 2 in septic mice.

As a Traditional Chinese Medicine, Melilotus extracts have been reported to function as an anti­inflammatory agent, antioxidant and inhibitor of capillary permeability. The present study aimed to identify the mechanisms by which Melilotus interferes with inflammation­associated and oxidative stress pathways during sepsis. An animal model of cecal ligation­perforation (CLP)­induced sepsis was established. Two hours prior to surgery, animals in the treatment group were administered 25 mg/kg Melilotus extract tablets and subsequently every 8 h. At 24 h post­administration, pathological modifications in lung tissue and expression levels of tumor necrosis factor­α­induced protein­8­like 2 (TIPE2) expression, nuclear factor (NF)­κB, toll­like receptor 4 (TLR4), heme oxygenase­1 (HO­1), inhibitor of κB kinase (IκB), pro­inflammatory mediators (interleukin­6 and tumor necrosis factor­α), myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), were examined. The results showed that Melilotus extract had a marked effect on the pathological manifestation of lung tissue and lung inflammatory response, the upregulation of TIPE2, HO­1 and IκB expression, and the inhibition of TLR4 and NF­κB activities. In addition, following treatment with Melilotus extract, the model animals demonstrated decreased levels of MPO and MDA as well as increased levels of SOD. In conclusion, these results indicated that Melilotus extract may be a potential therapeutic agent for the treatment of CLP­induced lung injury, the mechanism of which proceeded via inflammation­ and oxidation­associated pathways by increasing TIPE2 expression.

Rhodiola rosea suppresses thymus T-lymphocyte apoptosis by downregulating tumor necrosis factor-α-induced protein 8-like-2 in septic rats.

In recent years, several studies have shown that Rhodiola rosea can enhance cellular immunity and humoral immune function in mice, and thus, it has become a research hotspot. However, its underlying mechanism of action has remained elusive. The present study investigated whether Rhodiola rosea was able to downregulate the expression of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2), thereby inhibiting the expression of apoptotic genes, attenuating T-lymphocyte apoptosis and improving immunity in septic mice. A mouse model of caecal ligation and puncture (CLP)-induced sepsis was established, and animals in the treatment group were pre-treated with an intraperitoneal injection of Rhodiola rosea extract, while animals in the control group and sham-operated group were injected with an equivalent amount of normal saline. TIPE2, B-cell lymphoma 2 (Bcl-2), Fas and Fas ligand (FasL) mRNA and protein levels in thymic T cells were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Furthermore, the thymus T-lymphocyte apoptosis rate, thymus T-lymphocyte count and thymus T-lymphocyte sub-sets were assessed using flow cytometry. Levels of T-helper cell type 1 (Th1) cytokines [Interleukin (IL)-2, IL-12 and interferon (IFN)-γ] and Th2 cytokines (IL-4 and IL-10) were determined using ELISA. The results showed that, compared to that in the CLP group, the expression of TIPE2, Fas and FasL in the treatment group was significantly decreased, while the expression of Bcl-2 was increased (P<0.05). The thymus lymphocyte count in the CLP group was significantly higher compared with that in the treatment group (P<0.05). Furthermore, the apoptotic rate of thymus T-lymphocytes in the treatment group was significantly lower than that in the CLP group (P<0.05). In addition, treatment with Rhodiola rosea rescued decreased in the counts of the CD3(+) T and CD4(+) T sub-sets of thymus T lymphocytes in the CLP group (P<0.05), while not affecting the increased levels of Th2 cytokines (IL-4 and IL-10) in the CLP group compared with those in the control groups. In addition, the Th1 cytokines (IL-12, IL-2 and IFN-γ) were significantly increased (P<0.05) in the CLP group, and treatment with Rhodiola rosea led to further increases. The thymus index of septic mice treated with Rhodiola rosea as well as their survival rate were improved as compared with those in the CLP group. These findings suggested that Rhodiola rosea has protective effects against sepsis by decreasing apoptosis, increasing Th1 cytokines and enhancing the host's immunity via the regulation of TIPE2 expression.