Objective:To explore the effect of Toll-like receptor 9 (TLR9) signaling pathway activation on the transcriptome in the renal tubular cells.Methods:Mouse primary renal tubular epithelial cells were extracted and cultured. When the degree of cell fusion reached 80%, they were divided into two groups, which were added with 10 μL phosphate buffered saline (PBS, PBS control group) and TLR9 activator cytosine phosphate guanidine oligodeoxynucleotide (CpG-ODN) with a final concentration of 5 μmol/L (CpG-ODN treatment group). The RNA sequencing was performed on the Illumina platform after extraction. DEGseq software was used to analyze the differential expression of genes between the two groups. Goatools and KOBAS online software were used to analyze the differential genes involved signal pathways. Homer software was used to predict transcription factors.Results:Compared with the PBS control group, there were a total of 584 differentially expressed genes in the CpG-ODN treatment group, of which 102 were up-regulated and 482 were down-regulated. The most significantly enriched gene ontology (GO) terms of differentially expressed genes included response to interferon-β, defense response to virus and other inflammatory pathway. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways included 2'-5'-oligoadenylate synthase activity, regulation of ribonuclease activity, negative regulation of virus life cycle, cellular response to interferon-βand defense response to protozoan. The results of transcription factor prediction showed that interferon regulatory factor 3 (IRF3) was the most significantly enriched transcription factor in the promoter sequence of differential genes; the most significant transcription factor downstream of TLR9 was IRF3, and other predicted transcription factors such as transcription factor 21 (TCF21), zinc finger protein 135 (ZNF135), and PR domain containing 4 (PRDM4) might be new candidates for TLR9 signaling pathway.Conclusion:CpG-ODN activates TLR9 signaling pathway, and primary renal tubular epithelial cells can directly respond to CpG-ODN stimulation and undergo transcriptome changes, which provides a basis for further research on the molecular mechanism of TLR9 pathway in sepsis induced acute kidney injury.

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).
Adolescent ; Adult ; Age Factors ; Aged ; Antineoplastic Agents/adverse effects* ; Diabetes Mellitus/chemically induced* ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality* ; Young Adult

BACKGROUND: The biocompatibility of chitosan and Nafion can be improved by external factors. OBJECTIVE: To explore the effect of different weak laser irradiations (red, blue, green) on biocompatibility of porous chitosan membrane and the Nafion membrane. METHODS: (1) Porous chitosan membrane test: Forty-eight Sprague-Dawley rats were randomized into red, green, blue light groups (n=16 per group). Porous chitosan membranes (two membranes at each side) were implanted into the bilateral subcutaneous tissue of the rat back with the spine as the axis of symmetry, and then the four implanted membranes in each rat were irradiated by red light for 0, 2, 4, 6 minutes respectively. The irradiation lasted until sample collection at 7, 14, 28 and 56 days after implantation, and the samples were used for histological analysis. The same procedures were done in the blue and green light groups. (2) Nafion membrane test: Twenty-four Sprague-Dawley rats were randomized into red, blue and green light groups (n=8 per group). Nafion membranes (two membranes at each side) were implanted into the bilateral subcutaneous tissue of the rat back with the spine as the axis of symmetry, and then the four implanted membranes in each rat were irradiated by red light for 0, 2, 4, 6 minutes respectively. The irradiation lasted until sample collection at 7 and 14 days after implantation, and the samples were used for histological analysis. The same procedures were done in the blue and green light groups. RESULTS AND CONCLUSION: The content of red blood cells in blood vessels and vascular density around the membrane materials (porous chitosan membranes and Nafion membranes) increased after irradiated by red light (especially at 7 days after implantation); the red light had less influence on the inflammatory response and fibrous capsule thickness around the two kinds of membranes. The inflammatory cells percentage around the membrane materials irradiated by green light for 4 minutes was significantly reduced, and the blue light had less influence on inflammatory responses; blue and green lights showed effects on the fibrous capsule thickness and vascular density around the membrane materials, but the effect was not obvious. Thus, to a certain extent, weak lasers can improve the biocompatibility of PCSM and Nafion membrane.

BACKGROUND: Caspofungin, a novel echinocandins systemic antifungal agent, has been shown to exert broad-spectrum antibacterial effect on deep fungal infections, which is superior to or equivalent with the role of amphotericin B, but there is no report on its application for preventing fungal infection after renal transplantation.OBJECTIVE: To analyze the difference in high risk factors of fungal infection after kidney transplantation using donation after cardiac death donors and living-related donor kidney transplantations, and to explore the feasibility and safety of caspofungin to prevent fungal infection after kidney transplantation using donation after cardiac death donors.METHODS: This was a prospective, single-center, controlled trial finished at the Department of Kidney Transplantation,the First Affiliated Hospital of Zhengzhou University, Henan Province, China. Totally 188 patients undergoing primary kidney transplantation without history of fungal infection and use of antifungal drugs between January 2012 and August 2013 were enrolled, including kidney transplantation with donation after cardiac death donors (n=102, trail group), and kidney transplantation with living-related donors (n=86, control group). The CYP3A5 genotype was determined preoperatively. All patients received tacrolimus+mycophenolate mofetil+prednisone triple immunosuppression after transplantation. The trial group was subjected to caspofungin therapy for 2 weeks. The risk factors for fungal infection in the two groups were compared, and the effects of caspofungin on the tacrolimus concentration, tacrolimus concentration/dose were detected in the recipients with same CYP3A5 genotype recipients at 1 and 2 weeks, and 1, 3 and 6 months postoperatively. The liver and kidney function, adverse events and fungal infections were recorded at different time points. This trial was registered with the Chinese Clinial Trial Registry (Regitration number:ChiCTR-OON-17013342).RESULTS AND CONCLUSION: The survival rate of patient/kidney was 98.4% and 97.3% respectively, 97 cases in the trial group and 86 controls competed 6-month follow-up. Preoperative hemodialysis time, hemoglobin value, cold ischemia time, warm ischemia time, intraoperative blood transfusion volume, time of central venous catheter kept in situ,methylprednisolone usage, ATG usage, serum creatinine reduced level at 1 week, thrombocytopenia and duration of postoperative body temperature > 38 ℃ were the risk factors for fungal infection in the trail group relative to the control group. The fungal infection rate in the trial and control groups was 0% and 2.3%, respectively, at 6 months of follow-up.The serum creatinine level in the trail group was significantly higher than that in the control group at 1 month postoperatively (P < 0.05), and the level showed no significant difference between two groups at other time points (P >0.05). After 2 weeks of caspofungin treatment, the concentrations of tacrolimus and tacrolimus concentration/dosage did not differ significantly in different CYP3A5 genotype recipients (P > 0.05). Caspofungin might induce some adverse reactions, especially electrolyte disturbance with an incidence of 21.6%, but there was no significant difference between two groups (P > 0.05). These findings imply that kidney transplantation using donation after cardiac death donors presents with various risk factors for fungal infection compared with living-related donor kidney transplantation.Furthermore, caspofungin is effective and safe for preventing fungal infection and has no effect on tacrolimus concentration; therefore, it can be used as a new anti-fungal agent after kidney transplantation.

OBJECTIVE: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). METHODS: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. RESULTS: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=-4.39, p<0.001), were older (t=-4.69, p<0.001), reported more lifetime depressive episodes (z=-3.24, p=0.001), were more likely to experience seasonal depressive episodes (chi2=6.896, p=0.009) and depressive episodes following stressful life events (chi2=59.350, p<0.001), and were more likely to have a family history of psychiatric disorders (chi2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. CONCLUSION: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.
Anxiety* ; Asian Continental Ancestry Group ; Bipolar Disorder ; Checklist ; China ; Depression ; Depressive Disorder ; Depressive Disorder, Major* ; Humans ; Logistic Models ; Mood Disorders ; Risk Factors* ; Seasons

BACKGROUNDChronic kidney disease (CKD) is a growing public health problem with well-established risk factors. Other contributing factors, however, remain to be identified. Systemic inflammation in asthma plays a significant role in the development of other diseases. We therefore initiated a study to assess whether the growing prevalence of asthma is associated with an increase in the risk of CKD.

METHODSWe conducted a retrospective cohort study using data from 3015 patients with asthma aged 14 years and older who were registered and followed up in Asthma Control Study at the Department of Respiratory Medicine of three medical centers from 2005 to 2011. History, asthma control test (ACT), and asthma stage were used to assess the traits of asthma. CKD was defined as proteinuria and/or reduced estimated glomerular filtration rate (eGFR) (<60 ml×min(-1)×1.73 m(-2)) in two consecutive follow-up surveys. We used logistic regression models, adjusting for age, sex, and other confounding factor to determine associations between the traits of asthma and CKD. Kaplan-Meier curves were used to analyze patient outcomes.

RESULTSA total of 2354 subjects with complete data were recruited for this study with mean age (45.4±10.4) years. After 6 years of follow-up, 9.6% (n = 227) of the analytic cohort developed proteinuria and 3.1% (n = 72) progressed to eGFR <60 ml×min(-1)×1.73 m(-2). The patients with >20 years asthma history, not well-controlled or persistent asthma patients had higher incidence of proteinuria and reduced eGFR compared with patients with ≤20 years asthma history, at least well-controlled or remission asthma, respectively. The multivariable adjusted OR for proteinuria and reduced eGFR in participants with persistent asthma was 1.49; (95% confidence interval (CI) 1.17-1.91) and 2.07 (95% CI 1.34-4.42). Compared to patients with no asthma traits, there was a significant risk (OR, 3.39; 95% CI 1.36-8.73) for those who met all three traits, including asthma history >20 years, not well-controlled and persistent stage, after adjusting for potential confounding factors.

CONCLUSIONSIn this retrospective cohort study, we found that persistent asthma was associated with an increased risk of CKD, which was independent of obesity, diabetes, hypertension, and other well-established risk factors. Future studies should be directed to elucidate the mechanisms underlying the association between asthma and CKD.

Adult ; Asthma ; complications ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Renal Insufficiency, Chronic ; etiology ; physiopathology ; Retrospective Studies ; Risk Factors

Objective To construct the adeno-associated virus (AAV)vector of mouse carrying T-bet gene,which was applied to mouse model of asthma by nose,and to investigate the immunomodulatory effects of T-bet delivery on asthma.Methods Forty healthy Balb/c mice (aged 6-8 weeks) were randomly divided into 4 groups:control group (group A),asthma model group(group B),model/control recombinant adeno-associated virus carrying enhanced green fluorescent protein(rAAV-eGFP) intervention group (group C) and model/rAAV-T-bet virus intervention group(group D),with 10 mice in each group.In group B,group C,and group D,Balb/c mice were sensitized by intraperitoneal injection with OVA and challenged by nebulized OVA.In group C and group D,Balb/c mice were intervened with the isodose rAAV-eGFP and rAAV-T-bet,while in group B,the mice were intervened with the same amount of saline,both of them were dropped into the nasal cavity.Twenty-four hours after the last injection,the mice were sacrificed and the samples were obtained.The total cells in bronchoalveolar lavage fluid (BALF) were counted,and the types of cells were analyzed by Wright-Giemsa staining.The levels of interferon-γ (IFN-γ),IL-4 and IL-5 in BALF were determined by enzyme-linked immunosorbent assay.The expressions of T-bet,GATA-3 and Foxp3 protein in the lungs of asthmatic mice were detected with immunohistochemical technique.Results 1.The level of specific transcription factor T-bet in group B and group C were distinctly lower than that of group A (all P ＜ 0.05),while the level of GATA-3 was significantly higher than that of group A(all P ＜ 0.05).In group D,the expression of T-bet protein was stronger than that in group B and group C,however,the expression of GATA-3 decreased obviously (all P ＜ 0.05).The results of Foxp3 were similar to T-bet.2.In group D,the mice had suppressed levels of IL-4 [(158 ± 55) ng/L] and IL-5 [(68-± 22) ng/L] compared with those in group B and group C(all P ＜0.05).The level of IFN-γ[(113-±35) ng/L] increased compared with those in group B and group C (all P ＜ 0.05).At the same time,the number of total cells and eosinophil in BALF were both obviously lower than those of group B and group C (all P ＜ 0.05).Conclusions On the basis of building mouse model of asthma,intranasal administration of rAAV-T-bet can deliver T-bet gene to airway successfully and efficiently,and plays an immunomodulatory role in immune confusion of asthma.

OBJECTIVETo discuss the replantation of fingertip amputation in lack of availability of intravenous anastomosis.

METHODSFrom November 2009 to November 2010, 86 patients (104 fingers) with fingertip amputation were treated with replantatioin, including 64 males and 22 females, with an average age of 26 years ranging from 2 to 64 years. The time from injury to therapy was from 30 min to 12 h, time of broken finger ischemia was from 2.5 to 12 h. Preoperative examination showed no obvious abnormalities. Four different replantation methods were selectively applied to these 104 amputated fingertips of 86 cases: (1) replantation with anastomosis of single or bilateral proper digital artery in 37 fingers; (2) replantation with arteriovenous bypass in 27 fingers; (3) replantation with exclusive anastomosis of digital artery in 24 fingers; (4) replantation with removing the palmar pocket method in 16 fingers.

RESULTSOne hundred and two of 104 amputated fingertips were survived. Among these survived fingers,75 cases (92 fingers) were followed-up for 6 to 24 months. According to the assessment standard of Chinese Medical Association of Hand Surgery, the results were excellent in 52 cases, good in 19, poor in 4.

CONCLUSIONIt benefits to expand the indications and improve the survival rate of replantation of fingertip amputation with the correct choice of different replantation methods according to the injury situation of the broken fingertip artery after debridement under the microscope.

Adolescent ; Adult ; Amputation ; Child ; Child, Preschool ; Debridement ; Female ; Fingers ; physiology ; surgery ; Humans ; Male ; Middle Aged ; Recovery of Function ; Replantation ; methods ; Young Adult

Objective To understand the status of drinking-water-borne endemic fluorosis and the effect of preventive measure in Hebei province, so as to provide a basis to prevent and cure the disease. Methods Thirtyeight affected counties(cities, districts) with drinking-water-borne endemic fluorosis were sampled by random sampling in Hebei in 2009. All affected villages in every county were divided into mild, moderate and severe endemic fluorosis areas and a village was randomly selected from each category of the area to carry out the monitoring of endemic fluorosis. Dental fluorosis of children aged 8 - 12 were examined and 6 copies of urine samples were randomly collected in each age group in the above-mentioned villages. Clinical skeletal fluorosis was diagnosed among adults aged 16 and over and 20 copies of urine samples were tested for fluorosis in every village.Results A total of 112 affected villages were investigated, among which the drinking water quality of 66 villages were improved and 46 villages were not improved. A total of 236 copies of water samples from the 66 villages were measured and the fluoride content ranged from 0.1 to 4.3 mg/L, among which 20 copies of water samples exceeded the fluorine standard of 1.2 mg/L, accounting for 33.3%. A total of 230 copies of water samples were collected in the 46 villages and the fluoride content ranged from 0.2 to 4.6 mg/L, among which 76.1% (35/46) of the water samples exceeded the fluorine standard of 1.2 mg/L. A total of 5169 children aged 8 - 12 were examined of dental fluorosis, the dental fluorosis rate was 36.43%(1883/5169) and the dental fluorosis index was 0.81. A sum of 71 497 adults aged over 16 years were examined, and the rate of skeletal fluorosis was 4.81%(3438/71 497), moderate or severe clinical detection rate of skeletal fluorosis was 1.56%( 1114/71 497). A total of 2876 copies of children urine samples and 2021 copies of adult urine samples were tested and the geometric mean of fluoride content was 2.30,3.32 mg/L, respectively. Conclusions The prevalence of dental fluorosis of children in the areas with improved water is less than 30% and the rate of dental fluorosis and skeletal fluorosis decline gradually with time.The rate of dental fluorosis and skeletal fluorosis increases with the increase of water fluoride in the water quality not improved areas. The endemic fluorosis is still comparatively serious in Hebei. The progress of improving water quality in the areas with endemic fluorosis should be accelerated and the acceptability of improved water should be enhanced.

Previous studies demonstrated that interleukin-12 (IL-12) enhances the non-MHC-restricted cytotoxic activity of NK cells and facilitate specific allogeneic human cytotoxic T lymphocyte responses against fresh leukemia cells and cell lines. The Wilms' tumor gene, WT1 mRNA, has been used as a marker of minimal residual disease (MRD) for evaluating therapeutic efficacy of patients with leukemia or myelodysplastic syndrome (MDS). This study was aimed to investigate whether in vitro IL-12 can lower WT1 gene expression in peripheral blood monuclear cells (PBMNC) from patients with leukemia or MDS. PBMNC from these 30 patients and 5 healthy volunteers were cultured at 5 x 10(5) cells/ml alone with or without 100 units/ml of IL-12 for 3 days. WT1 mRNA was measured by competitive reverse transcription polymerase chain reaction (RT-PCR) since WT1 mRNA is considered as a marker of minimal residual disease (MRD) in leukemia and MDS. The results demonstrated that WT1 mRNA in PBMNC of 5 healthy volunteers was less than 10(3) copies/microg of total RNA. Following the 3-day IL-12 treatment, mean WT1 mRNA of PBMNC was reduced from 10(4.8) to 10(4.2) copies/microg of total RNA in 6 CML patients, from 10(5.4) to 10(4.8) copies/microg in 12 MDS patients and from 10(5.0) to 10(4.2) copies/microg in 5 AML patients in CR, but not reduced in 5 of 7 AML in non-CR. It is concluded that IL-12 significantly decrease the quantity of leukemia cells in PBMNC of most patients with MDS, CML and AML in CR. IL-12 may be of considerable benefit in the elimination of MRD in patients with hematological malignancies.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Interleukin-12 ; pharmacology ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; metabolism ; Neoplasm, Residual ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; WT1 Proteins ; biosynthesis ; genetics