Objective To explore the biological functions of retinoic acid-inducible gene-I(RIG-I) in vivo through phenotype analysis of RIG-I knockout mice. Methods The gene expression of RIG-Ⅰ in various tissues of mice was examined with Northern blotting and semi-quantitative RT-PCR.The phenotypes observed included body weight measurement,differential count of peripheral blood cells,metabolic parameters measurement and histopathologic examination. ResultsRIG-Ⅰ expressed in various tissues of mice with different levels.No gross developmental abnormalities and expected maturation arrest in granulocytic differentiation were observed in RIG-Ⅰ knockout mice.However,RIG-Ⅰ knockout mice exhibited an unexpected increase in the ratios of neutrophiles to lymphocytes in peripheral blood and increased susceptibility to bacteria infection. Conclusion RIG-Ⅰ may play an important role in immune regulation in mice.

OJBECTIVETo investigate the predictive value of the qualitative assessment of general movements (GMs) for adverse outcomes at 24 months of age in full-term infants with asphyxia.

METHODSA total of 114 full-term asphyxiated infants, who were admitted to the neonatal intensive care unit between 2009 and 2012 and took part in follow-ups after discharge were included in the study. All of them received the qualitative assessment of GMs within 3 months after birth. The development quotient was determined with the Bayley Scales of Infant Development at 24 months of age.

RESULTSThe results of the qualitative assessment of GMs within 3 months after birth showed that among 114 infants, 20 (17.5%) had poor repertoire movements and 7 (6.1%) had cramped-synchronized movements during the writhing movements period; 8 infants (7.0%) had the absence of fidgety movements during the fidgety movements period. The results of development quotient at 24 months of age showed that 7 infants (6.1%) had adverse developmental outcomes: 6 cases of cerebral palsy and mental retardation and 1 case of mental retardation. There was a poor consistency between poor repertoire movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=-0.019; P>0.05). There was a high consistency between cramped-synchronized movements during the writhing movements period and the developmental outcomes at 24 months of age (Kappa=0.848; P<0.05), and the results of predictive values of cramped-synchronized movements were shown as follows: predictive validity 98.2%, sensitivity 85.7%, specificity 99.1%, positive predictive value 85.7%, and negative predictive value 99.1%. There was a high consistency between the absence of fidgety movements during the fidgety movements period and the developmental outcomes at 24 months of age (Kappa=0.786; P<0.05), and its predictive values were expressed as follows: predictive validity 97.4%, sensitivity 85.7%, specificity 98.1%, positive predictive value 75.0%, and negative predictive value 99.1%.

CONCLUSIONSCramped-synchronized movements and absence of fidgety movements can predict adverse developmental outcomes at 24 months of age in full-term infants with asphyxia.

Asphyxia Neonatorum ; physiopathology ; Child Development ; Humans ; Infant ; Infant, Newborn ; Movement ; Predictive Value of Tests ; Qualitative Research

Objective To observe the acute toxicity and long -term toxicity induced by Chuanping dropping pills in beagle dogs.Methods Acute toxicity test:it was used by the approximate lethal dose on Beagle dogs.Observational index included general clinical observation, weight, ingestion capacity, blood pressure, electrocardiogram, urinalysis, blood test, blood biochemical examination and pathological examination.Long-term toxicity test:Chuanping dropping pills with 0.13, 0.40, 1.19 g · kg-1 · d-1 and the hollow capsules control group in Beagle dogs were lavaged.Observational index included general physiological indices, blood test,blood biochemical examination, urinalysis, electrocardiogram, blood pressure, eye test and pathological examination.Results The approxi-mate lethal dose in beagle dogs lavaged by Chuanping dropping pills was more than 54.79 g · kg-1.Relativel safe dose in Beagle dogs lavaged by Chuanping dropping pills after 90 days was below 0.40 g · kg-1 · d-1.Conclusion Clinical dose of Chuanping dropping pills was safe and reliable.

The aim of the present study was to determine whether angiotensin-converting enzyme inhibitors (ACEI) could contribute to the protective effects of preconditioning, and to explore its underlying mechanism. The Langendorff model of isolated rat heart was used. Cardiac contractility and lactate dehydrogenase (LDH) in the coronary effluent were measured, and infarct area of hearts after 30 min of ischemia followed by 120 min of reperfusion was analyzed. We found that: (1) The subthreshold preconditioning (2 min of ischemia and 10 min of reperfusion), captopril (an ACEI with sulfhydryl groups) or perindoprilate (an ACEI without sulfhydryl groups) alone did not protect the hearts from being injured by 30 min of ischemia and 120 min of reperfusion. (2) However, the combination of captopril or perindoprilate with subthreshold preconditioning could decrease left ventricular end-diastolic pressure (LVEDP), increase left ventricular developed pressure (LVDP) and coronary flow compared with the subthreshold preconditioned group. The combination treatments also inhibited the release of LDH from ischemia/reperfusion hearts, and reduced the infarct area in ischemic heart after 2 h of reperfusion (P<0.05). (3) By using NOS inhibitor L-NAME (100 mumol/L) before combined administration of ACEI with subthreshold preconditioning, the protection effect triggered by the combination treatment was significantly reduced. Pretreatment of the hearts with mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel inhibitor 5-HD (100 mumol/L) also abolished the protection effect (P<0.05). (4) Subthreshold preconditioning, captopril or perindoprilate alone could enhance the NO content in coronary effluent (P<0.05), but the combination of captopril or perindoprilate with subthreshold preconditioning could further augment the NO content compared with the subthreshold preconditioned group (P<0.05). The results indicate that ACEIs with or without sulfhydryl groups may potentiate the subthreshold preconditioning to trigger cardiac protection effect against the ischemia/reperfusion injury. This protection effect in the heart is possibly mediated by the generation of NO and the activation of mitoK(ATP) channel.

Poly（ADP-ribose）polymerase（PARP）is a kind of DNA damage repair enzyme. PARP inhibitors include Olaparib （AZD2281），Niraparib（MK-4827），Rucaparib，Veliparib（ABT-888），Fluzoparib and Talazoparib （BMN-673），etc. This article reviews the preclinical research on the combined application of PARP inhibitors against tumor by searching the relevant literatures. Through the synthetic lethal mode ，PARP inhibitors have a strong killing effect on tumor cells with homologous recombination repair defects. However ，for tumor cells with intact DNA damage repair function ，PARP inhibitors often need to be combined with radiotherapy or other drugs to play a role. Combined application drugs include antiangiogenic drugs ，heat shock protein 90 inhibitors，cyclin-dependent kinase 12 inhibitors，immune checkpoint inhibitors ，histone deacetylase inhibitors ，etc. The combined application of PARP inhibitors is expected to enhance the efficacy of anti-tumor drugs and achieve the goals of sensitization ， synergism and reversal of drug resistance ，which is worthy of further in-depth research and exploration of new combined treatment schemes.

The purpose of this study was to investigate the efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and its related technologies in hematological malignancies. 26 patients with hematological malignancies (acute leukemia 10, chronic myeloid leukemia 14, multiple myeloma 2) received allo-NST following conditioning regimens with fludarabine/cyclophosphamide/ATG in 14 cases or busulfan or melphalan/cyclophosphamide/ATG in 12 cases prior to infusion of 2 or 3 collections of G-CSF (600 microg/d) or G-CSF (300 microg/d) plus GM-CSF (300 microg/d) mobilized blood stem cell on the fifth day. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients were eligible for donor lymphocyte infusion (DLI) (or donor stem cell infusion (DSI)) given in graded increments according to the chimeric formation and clinical feature. Generally, the dose of the first infusion was 1 x 10(7)/kg in 4th week post-transplantation. The engraftment analyses included the detection of microsatellite short tandem repeats (STRs), bcr/abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that out of 26 patients, 22 (84.62%) were engrafted, 18/22 were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 (11.54%), while chronic GVHD was diagnosed in 6 out of 26 (23.07%) patients. The incidence and degree of infection and hemorrhage were low and slight. It is concluded that NST is a safe and effective therapy for hematological malignancies, whereas related technologies such as adaptation selected, conditioning regimen and transplantation immunotherapy should be studied further.
Adult ; China ; epidemiology ; Female ; Graft vs Host Disease ; epidemiology ; Hematologic Neoplasms ; therapy ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; adverse effects ; methods ; Transplantation Conditioning ; methods

OBJECTIVETo investigate the role of Snitrosylation of protein disulphide isomerasec in methamphetamine (METH)-induced expression of alpha synuclein (αSN) in mouse hippocampus and striatum neurons.

METHODSForty C57BL/6 mice were randomized equally into saline control group, METH group, L-NNA (a NOS inhibitor) group and L-NNA plus METH group. All the agents were injected intraperitoneally at an interval of 12 h, and a total of 8 injections were administered; in L-NNA plus METH group, METH was injected 30 min after LNNA in each treatment. Western Blotting was used to detect the expression of nitric oxide synthase (NOS), αSN, PDI and Snitrosylation of protein disulphide isomerase (PDI-SNO) in the hippocampus and striatum of the mice, and nitric oxide (NO) levels were determined using a NO assay kit.

RESULTSIn METH group, the levels of NOS, PDISNO, αSN and NO all increased significantly compared with those in the control group (P<0.05). Combined treatment with L-NNA and METH, compared with METH alone, resulted in significantly lowered expression of NOS, NO, PDI-SNO and αSN in the hippocampus and striatum of the mice (all P<0.05). No significant differences were found in NOS, NO, PDI-SNO or αSN expressions among METH+L-NNA, L-NNA and control groups (P>0.05).

CONCLUSIONMETH induces the activation of NOS and increases NO level to cause the occurrence of PDI-SNO, leading subsequently to increased expression of αSN in mouse striatum and hippocampus. L-NNA, the inhibitor of NOS, can partly relieve nervous system toxicity induced by METH.

OBJECTIVESTo measure serum and follicular resistin, steroids hormone levels in women with PCOS (polycystic ovary syndrome) (BMI (body mass index)<25 kg/m(2)), to assess possible correlations of resistin to hormonal and metabolic parameters and to analyze the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with PCOS and tubal infertility.

STUDY DESIGNWe analyzed the clinical outcomes of IVF-ET in women with PCOS (BMI<25 kg/m(2)) and tubal infertility during the years 2002 to 2004 and compared the serum and follicular fluid resistin levels, estradiol (E(2)), progesterone (P), testosterone (T) levels in 20 PCOS and 20 healthy, age-matched women without PCOS during IVF-stimulated cycles. The correlations between the resistin levels and the outcomes of IVF-ET were evaluated.

RESULTSNo significant differences in resistin levels of either serum or follicular fluid between PCOS and control group were found. However, resistin levels in serum were higher than that in follicular fluid in both groups. Multiple regression analysis showed that resistin levels in serum did not correlate with BMI, estradiol, LH (luteinizing hormone) and insulin level in fasting blood. No significant correlations were found between follicular fluid reisistin levels and fertilization rate, implantation rate, clinical pregnancy rate or early miscarriage rate in both PCOS and control groups.

CONCLUSIONOur results show that resistin does not have correlation with the hormonal and metabolic parameters as well as the outcomes of IVF. These data suggest that resistin is unlikely to be a local determinant factor in steroidogenesis and growth and maturation of oocytes during IVF-ET in lean women with PCOS.

Adult ; Case-Control Studies ; Embryo Transfer ; Female ; Fertilization in Vitro ; Follicular Fluid ; metabolism ; Gonadal Steroid Hormones ; blood ; metabolism ; Humans ; Infertility, Female ; blood ; etiology ; metabolism ; therapy ; Polycystic Ovary Syndrome ; blood ; complications ; metabolism ; therapy ; Pregnancy ; Pregnancy Outcome

This study was a single-center large-sample case-control study.Data of 1 106 elderly patients who underwent unilateral total hip arthroplasty from June 2013 to May 2019 were collected, including items such as patient′s baseline characteristics, comorbidities, perioperative medication, intraoperative blood pressure, and postoperative outcomes.Patients were divided into postoperative nausea and vomiting(PONV)group and non-PONV group according to whether nausea and vomiting occurred within 24 h after operation.Logistic regression analysis was used to determine the risk factors for PONV.The incidence of PONV was 11.03%.Female, intraoperative use of dezocine, and intraoperative hypotension(duration>3 min or cumulative time>6 min)are independent risk factors for PONV, while femoral neck fractures and intraoperative use of dexamethasone are protective factors.

In order to investigate the clinical efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and related technology in patients with hematologic malignancies, twenty-six cases of hematological malignancies (10 AL, 14 CML, 2 MM patients) received NST following conditioning regimens with fludara + cyclophosphamide + ATG (14 cases) and busulfan or melphalan + cyclophosphamide + ATG (12 cases), G-CSF (600 micro g/d) or G-CSF (300 micro g/d) + GM-CSF (300 micro g/d) were used for mobilizing peripheral blood stem cell. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients will be eligible for donor lymphocyte infusion (DLI) or donor stem cell infusion (DSI) given in graded increments according to the chimeric formation and clinical reaction. Generally the dose of the first infusion was 1 x 10(7)/kg at 4th week post-transplantation. The engraftment analysis included the detection of microsatellite short tandem repeats (STRs), Bcr/Abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that 22 patients (84.62%) were engrafted, among which 18 patients were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 cases (11.54%). Chronic GVHD was diagnosed in 6 of 26 (23.07%) evaluable patients. The incidence of infection and hemorrhage was low and slight. It is concluded that allo-NST is a safe and effective therapeutic method for hematologic malignancies, but the related technology such as selection of indication, conditioning regimen and transplantation immunotherapy should be studied further.
Adult ; Cytomegalovirus Infections ; etiology ; Female ; Graft vs Host Disease ; etiology ; Hematologic Neoplasms ; therapy ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Transplantation, Homologous