[Epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023].

Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023. Methods: The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed. Results: A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M (Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant (P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age (P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion: Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Correlation between primary family caregiver identity and maternal depression risk in poor rural China.

INTRODUCTION: Prenatal and postpartum depression are important public health challenges because of their long-term adverse impacts on maternal and neonatal health. This study investigated the risk of maternal depression among pregnant and postpartum women in poor rural China, along with the correlation between primary family caregiver identity and maternal depression risk. METHODS: Pregnant women and new mothers were randomly selected from poor rural villages in the Qinba Mountains area in Shaanxi. Basic demographic information was collected regarding the women and their primary family caregivers. The Edinburgh Postnatal Depression Scale was used to identify women at risk of depression, and the Perceived Social Support Scale was used to evaluate perceived family support. RESULTS: This study included 220 pregnant women and 473 new mothers. The mean proportions of women at risk of prenatal and postpartum depression were 19.5% and 18.6%, respectively. Regression analysis showed that identification of the baby's grandmother as the primary family caregiver was negatively correlated with maternal depression risk (ß=-0.979, 95% confidence interval [CI]=-1.946 to -0.012, P=0.047). However, the husband's involvement in that role was not significantly correlated with maternal depression risk (ß=-0.499, 95% CI=-1.579 to 0.581, P=0.363). Identification of the baby's grandmother as the primary family caregiver was positively correlated with family support score (ß=0.967, 95% CI=-0.062 to 1.996, P=0.065). CONCLUSION: Prenatal and postpartum depression are prevalent in poor rural China. The involvement of the baby's grandmother as the primary family caregiver may reduce maternal depression risk, but the husband's involvement in that role has no effect.

[Research progress of C-X-C motif chemokine ligand 12 and its receptor signaling axis in the regulation of pulmonary fibrosis].

Pulmonary fibrosis is an irreversible interstitial lung disease characterized by lung parenchyma remodeling and collagen deposition. In recent years, the incidence and mortality of pulmonary fibrosis caused by unknown causes have risen. However, its pathogenesis is still unclear. C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor 4 (CXCR4)/CXCR7 signal axis plays a critical regulatory role in pulmonary fibrosis disease. In addition, the signal axis has been shown to regulate recruitment and migration of circulating fibrocytes, mesenchymal stem cells to the damage lung tissue, the migration of endothelial cells, the proliferation and differentiation of fibroblasts and endothelial cells, which further affects the occurrence and progression of pulmonary fibrosis. In this review, we summarized the pathogenesis and treatment research progress of CXCL12 and its receptor CXCR4/CXCR7 in the occurrence and progression of pulmonary fibrosis.

[Early clinical efficacy analysis of personalized three-dimensional printing talus prosthesis in the treatment of collapse talus necrosis].

Object To examine the preliminary clinical efficacy of custom-made three-dimensional(3D) printed talus prosthesis in the treatment of collapse talus necrosis. Methods: The clinical data of 8 patients who received 3D printed custom-made talus prostheses replacement for severe collapsed necrosis of the talus at the Orthopaedic Sports Medical Center, the First Affiliated Hospital to Army Medical University were analyzed retrospectively.All patients were male,with an average age of 38.0 years (range:22 to 65 years).There were 5 cases of left talus collapse and 3 cases of right talus collapse,with the course of disease of 29.7 weeks (range:6 to 96 weeks).The CT data of contralateral healthy talus were used for mirror image design references for the prosthesis,and the electron-beam 3D printing technology was used to prepare the prosthesis.Titanium alloy (Ti6Al4V) was taken as the material for the preparation of the talus body prosthesis,and Co-Cr-Mo material was used as the material for the preparation of the tibialis talus lateral joint surface prosthesis,and the subtalar joint surface of the prosthesis was made from a microporous casting technique.The prosthesis was analyzed preoperatively by digital three-dimensional finite element analysis and solid comparison techniques to measure anatomic match of the prosthesis.A longitudinal incision on medial ankle was made.The necrotic talus was completely removed and the prosthesis was then implanted.The patient was reexamined in the outpatient department 3, 6, and 12 months after surgery.Primary outcome measures were the American Orthopaedic Foot and Ankle Society(AOFAS) ankle-hind foot score,visual analogue scale(VAS) and ankle range of motion.Changes in imaging data and plantar pressure were also assessed.Repeated measures analysis of variance and paired-t test were used to compare the data. Results: The talus prosthesis measure preoperatively was completely consistent with that contralateral healthy talus and there was no operation-related complication. All the wounds healed primarily. The patients were followed up effectively for 23.17 months (range:12 to 48 months).The preoperative dorsiflexion of patients was (7.6±5.7)°,it increased to(14.2±6.6)° at 12 month after surgery (t=-2.67,P=0.03).The plantar flexion increased from (22.0±9.9)°preoperatively to (29.2±8.7)° at 12 month after surgery (t=-8.95,P<0.01).Preoperative AOFAS ankle-hind foot score was 26.3±6.6,and it increased to 70.1±2.2,76.0±3.4 and 79.3±4.2 at 3 month,6 month and 12 month after surgery(F=56.81,P<0.01);Pre-operative VAS was[M(QR)]3.0(0.8),and it increased to 2.5(1.0),1.5(1.0),1.0(1.0)at 3 month,6 month and 12 month after surgery(F=20.00,P<0.01).At the last follow-up,imaging reexamination showed that the prosthesis of all patients were in stable position with no sign of subsidence.No secondary ankle fusion or revision was required.The talus height increased from (27.6±6.0)mm preoperatively to (34.6±3.5)mm (t=-2.94,P<0.01).The plantar pressure showed that the maximum pressure on the healthy ankle was(629.9±26.1)N,and that on the affected side was(521.4±14.4)N.The pressure on the healthy ankle was(350.6±29.6)N,and that on the necrotic side was (212.3±9.7)N.The load on the contralateral forefoot was(38.1±2.8)% and that on the necrotic side was(11.5±2.0)%.The load on the contralateral hindfoot was (24.6±2.5)% and that on the necrotic side was (21.1±1.8)%. Conclusions: The custom-made 3D printed talus prosthesis could restore the talus anatomy,recover the ankle joint function,relieve the pain of patients and improve the life quality of patients.The effect on plantar pressure is mainly achieved by adjusting the center of gravity of plantar pressure backwards and the increase of weight bearing of the healthy foot.

Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: comparison of treatment efficacy, safety and quality of life.

OBJECTIVE: This present study aimed to compare the treatment response, survival profile, quality of life (QoL), and safety between drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) and chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Totally, 44 advanced NSCLC patients were analyzed retrospectively and were divided into DEB-BACE group (n=23) and chemotherapy group (n=21). Treatment response, European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30), progression-free survival (PFS), overall survival (OS), and adverse events were assessed during the follow-up. RESULTS: At month (M) 2, M4 and M6 post initial treatment, objective response rate (ORR) was elevated (all p <0.05), and disease control rate (DCR) tended to be higher (without statistical significance) in DEB-BACE group compared with chemotherapy group. Regarding the QLQ-C30 item scores, the scores of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning were increased, while the scores of nausea and vomiting, dyspnea, constipation were decreased in DEB-BACE group compared with chemotherapy group (all p <0.05). Based on survival profile, DEB-BACE group achieved better PFS and OS compared with chemotherapy group independent of TNM stage, which was also supported by further subgroup analysis and Cox's proportional hazard regression analysis (all p <0.05). Furthermore, two groups all exhibited mild and tolerable adverse events. CONCLUSIONS: DEB-BACE has the potential to be an additional treatment option with favorable therapeutic efficacy, improved QoL, and tolerable safety for advanced NSCLC patients.

[Impact of low T3 syndrome on adverse cardiovascular events in adult patients with acute viral myocarditis].

Objective: To determine the impact of low T3 syndrome on adverse cardiovascular events in adult patients with acute viral myocarditis. Methods: The study population consisted of 134 consecutive patients admitted between January 2002 and March 2018 with diagnoses of acute viral myocarditis (onset of symptoms<1 month,patients were divided into low serum free triiodothyronine (FT3, n=20) group and normal FT3 (n=114) group. General information, clinical presentation,electrocardiography at admission,laboratory tests,echocardiography features were analyzed. Low T3 syndrome was defined as a state with decreased FT3 and total triiodothyronine (TT3), normal or decreased free thyroxine (FT4) and total thyroxine (TT4) as well as normal thyroid stimulating hormone (TSH). Composite adverse cardiovascular events included death, persistent ventricular tachycardia (VT) or ventricular fibrillation (VF) and cardiac arrest. Risk factors related with composite adverse cardiovascular events in adult patients with acute viral myocarditis were analyzed by logistic regression analysis. Results: Systolic blood pressure was significantly lower (P<0.01),while heart rate (P=0.004) and the prevalence of VT/VF were significantly higher (P=0.017) in low T3 group than in the normal T3 group. Level of white blood cell,C response protein,fasting glucose (all P<0.01) as well as creatinine (P=0.035) were significantly higher, while level of FT3 and left ventricular ejection fraction (LVEF) were significantly lower (both P<0.01) in low T3 group than in normal T3 group. Multivariate logistic regression analysis revealed that LVEF at admission less than 40% (OR=6.615,95%CI 1.186-36.907, P=0.031) and FT3 level less than 1.79 ng/L (OR=9.131, 95%CI 1.577-52.857, P=0.014) were independent risk factors of increased composite adverse cardiovascular events in patients with acute viral myocarditis. Conclusion: Low FT3 increases the risk of adverse cardiovascular events in adult patients with acute viral myocarditis.

[Effects of blueberry on hepatic fibrosis and expression of nuclear transcription factor-кB in rats].

Objective: To observe the effects of blueberry and nuclear expression of transcription factor-кb (NF-кb) p65 in an experimental rat model of liver fibrosis. Methods: Forty-five Sprague-Dawley rats were randomly divided into isotonic saline control group (A); model group (B); blueberry juice prevention group (C, 15 g/kg); dan-shao-hua-xian capsule prevention group (D, 1 g/kg); and blueberry juice + dan-shao-hua-xian capsule prevention group (E). Rat liver fibrosis model was established by covalent compound carbon tetrachloride (CCl(4)). Each prevention group was given the corresponding dose of blueberry juice or (and) dan-shao-hua-xian capsule, and the rats were sacrificed after 8 weeks. The degree of liver fibrosis was evaluated by hematoxylin and eosin stain. A liver tissue of NF-κBp65 was detected by immunohistochemical method. The NF-κBp65 protein expression of liver tissue and transforming growth factor (TGF) ß1 was detected by Western blot. Data of multiple groups were compared by one-way analysis of variance, and rank sum test. Results: Immunohistochemistry detected that TGFß1 protein was mainly expressed in mesenchymal origin of hepatic stellate cells. The expression level of group A (3.75 ± 1.67) was low, while those of group B (9.00 ± 2.07), C (7.33 ± 1.00), D (6.00 ± 1.51), and E (3.5 ± 1.41) were high. However, the expression level of TGF-ß1 protein in hepatic tissues of group B was significantly higher than that of group C, D and E [group E: 3.5 ± 1.41, F = 18.350, P < 0.05]. In addition, group D was higher than group E (P < 0.05). The expression of NF- kappa Bp65 protein was very complex, and the expression patterns in different groups were different (Statistical calculation of experimental data were based on expression of liver cells). Compared with group B (4.37 ± 2.13), the relative expression levels of NF-κBp65 protein in-group A (0.46 ± 0.25), group C (2.76 ± 1.01), group D (2.13 ± 1.51), group E (1.88 ± 0.99) were significantly decreased (F = 27.490, P < 0.05), and the expression trend was consistent with TGFß1 protein. Western blot detected NF-κBp65 protein in liver tissues of rats. Compared with group A, levels in groups B, C, D and E were significantly increased (F = 96.983, P < 0.05), and groups C, D and E were significantly lower. The E group was significantly lower than the C group (F = 96.983, P < 0.05), and the degree of hepatic fibrosis was lower in each prevention group than in the B group (T = 24.1, P < 0.05). Conclusion: Blueberries have preventive effect on CCl4-induced hepatic fibrosis in rats, and its preventive mechanism may inhibit the expression and activation of NF-κBp65 in hepatocytes, thereby reducing TGFß1- mediated production or activation.

Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014.

BACKGROUND: Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. METHODS: We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. RESULTS: Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. CONCLUSION: INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes.

Genome-wide identification and expression analysis of CIPK genes in diploid cottons.

Calcineurin B-like protein-interacting protein kinase (CIPK) plays a key regulatory role in the growth, development, and stress resistance of plants by combining with phosphatase B subunit-like protein. In the present study, CIPK genes were identified in the whole genomes of diploid cottons and their sequences were subjected to bioinformatic analyses. The results demonstrated that the CIPK gene family was unevenly distributed in two diploid cotton genomes. Forty-one CIPKs were identified in the D genome, mainly located on chromosomes 9 and 10, whereas thirty-nine CIPKs were identified in the A genome, mainly located on chromosomes 8 and 11. Based on the gene structures, CIPKs in cotton could be classified into two types: one that is intron-rich and the other that has few introns. Phylogenetic analysis revealed that the CIPK gene family members in cotton had close evolutionary relationships with those of the dicotyledonous plants, such as Arabidopsis thaliana and poplar. The analysis of transcriptome sequence data demonstrated that there were differences in gene expression in different tissues, indicating that the expression of the CIPKs in cotton had spatio-temporal specificity. The expression analysis of CIPKs under abiotic stresses (drought, salt, and low temperature) in different tissues at trefoil stage demonstrated that these stresses induced the expression of CIPKs.

Comparative study of neural differentiation of bone marrow mesenchymal stem cells by different induction methods.

Neurogenic differentiation of bone marrow (BM) mesenchymal stem cells (MSCs) offers a new hope for patients with many neurological disorders. Several chemical inducers are employed to induce BMMSCs differentiation into nerve cells. In the present study, we compared different inducers [2-mercaptoethanol (BME), tretinoin (ATRA), dimethyl sulfoxide/butylated hydroxyanisole (DMSO/BHA), and indomethacin/3-isobutyl-1-methylxanthine (indomethacin/IBMX)] on the neurogenic differentiation of BMMSCs and aimed to identify a more efficient and safer method. The MSCs were first identified by their ability to adhere to plastic and by the expression of positive (CD44, CD90, and CD105) and negative (CD34) markers assessed by flow cytometry. The efficiency of the neurogenic differentiation was determined by assessing the mRNA and protein expression of nestin, microtubule-associated protein-2 (MAP2), neuron specific enolase (NSE), and glial fibrillary acidic protein (GFAP) by reverse transcription-polymerase chain reaction and western-blot, respectively. The effect of these inducers on cell viability was also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. This comprehensive study shows that indomethacin/IBMX is better than BME, DMSO/BHA, and ATRA both in terms of efficiency and safety, while BME suppressed the growth and proliferation of MSCs.

Birth weight and risk of coronary heart disease in adults: a meta-analysis of prospective cohort studies.

Some studies have found a significant relationship between birth weight (BW) and the risk of coronary heart disease (CHD) in adulthood, but results were inconsistent. The purpose of this study was to characterize the association between BW and the risk of CHD in adults. Among 144 papers detected by our search, 27 papers provided data on the relationship between BW and CHD, of which 23 papers considered BW as a continuous variable, and 14 articles considered BW as a categorical variable for this meta-analysis. Based on 23 papers, the mean weighted estimate for the association between BW and the combined outcome of non-fatal and fatal CHD was 0.83 [95% confidence interval (CI), 0.80-0.86] per kilogram of BW (P<0.0001). Low birth weight (LBW<2500 g) was associated with increased risk of CHD [odds ratio (OR), 1.19; 95% confidence interval (CI), 1.11-1.27] compared with subjects with BW⩾2500 g. LBW, as compared with normal BW (2500-4000 g), was associated with increased risk of CHD (OR, 1.16; 95% CI, 1.08-1.25). High birth weight (HBW⩾4000 g) was associated with decreased risk of CHD (OR, 0.89; 95% CI, 0.81-0.98) compared with subjects with BW<4000 g. In addition, there was an indication (not quite significant) that HBW was associated with a lower risk of CHD (OR, 0.89; 95% CI, 0.79-1.01), as compared with normal BW. No significant evidence of publication bias was present. These results suggest that LBW is significantly associated with increased risk of CHD and a 1 kg higher BW is associated with a 10-20% lower risk of CHD.

Pathology of the annular ligament in paediatric Monteggia fractures.

OBJECTIVES: To report our operative findings regarding the annular ligament in paediatric Monteggia fractures and to propose treatment recommendation for Monteggia fracture. PATIENTS AND METHODS: A total of 35 children with type I and type III Monteggia fractures were treated operatively. The radial heads were all explored surgically in this series. The interposed ligament was stretched out of the joint space and was reduced around the radial head. In some of the patients, the joint capsule was repaired. Sixteen ulnar fractures were managed with open reduction and wire fixation, and 13 broken ulnas were fixed by plating. Six ulnar fractures were greenstick type and were treated by closed reduction and external fixation. RESULTS: All the patients were functionally excellent at the 6-month follow-up in terms of bone healing and the range of motion of the elbow joint. No redislocation or subluxation of the radial head was found until in the last follow-up. No heterotropic ossification was observed in any follow-up radiographs. CONCLUSIONS: The annular ligaments were intact in all paediatric patients with type I and type III Monteggia fractures and the ruptures were transversely on the joint capsule at the lower margin of the ligament. Most of the annular ligaments were interposed in the radiohumeral joint even though the radiographs showed reduction of the radial heads. We recommend reduction of the annular ligament in paediatric patients with Monteggia fractures.

Abdominal computed tomographic findings of Mycobacterium tuberculosis and Mycobacterium avium intracellulare infection in HIV seropositive patients.

OBJECTIVE: To compare the computed tomographic (CT) findings of abdominal Mycobacterium tuberculosis (MTB) infection and Mycobacterium avium intracellulare (MAI) infection in patients with human immunodeficiency virus (HIV) infection. METHODS: A retrospective review of the CT findings of 30 patients with HIV and proven MTB (n = 9) or MAI (n = 21) infection was conducted. Images were reviewed by a radiologist blinded to the diagnosis, and the radiologic findings involving the abdominal viscera, peritoneum and lymph nodes were compared. RESULTS: The following were more frequent in patients with MAI infection: hepatomegaly (MAI 71% v. MTB 44%, p < 0.05), uniform attenuation of lymph nodes (MAI 90% v. MTB 55%, p < 0.05) and clustered pattern of lymph nodes (MAI 57% v. MTB 22%, p < 0.05). In patients with MTB infection, lymph nodes with low attenuation centrally were more common (MAI 10% v. MTB 44%, p < 0.05), and mesenteric lymph nodes were significantly larger (MAI mean = 20 mm v. MTB mean = 40 mm, p < 0.05). CONCLUSION: Although nonspecific, CT may be useful in the early diagnosis of MTB and MAI infection, allowing for presumptive treatment before microbiologic confirmation.

The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells.

The effect of quercetin on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied. Quercetin pretreatment significantly inhibited NO production in an LPS-stimulated RAW 264.7 murine macrophage cell line. Post-treatment with quercetin partially inhibited NO production. The inhibitory action of quercetin was due to neither the cytotoxic action nor altered LPS binding. The expression of inducible-type NO synthase (iNOS) was markedly down-regulated by quercetin. Quercetin suppressed the release of free nuclear factor (NF)-kappaB by preventing degradation of IkappaB-alpha and IkappaB-beta. Moreover, quercetin blocked the phosphorylation of extracellular signal regulated kinase 1/2 (Erk 1/2), p38, and c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and, further, the activity of tyrosine kinases in LPS-stimulated RAW cells. Quercetin also inhibited interferon (IFN)-gamma-induced NO production. Taken together, these results indicate that the inhibitory action of quercetin on NO production in LPS- and/or IFN-gamma-stimulated macrophages might be due to abrogation of iNOS protein induction by impairment of a series of intracellular signal pathways.

The expression of membrane-bound CD14 renders mouse B-1 cells susceptible to LPS.

The surface expression of CD14 on mouse B-1 cells and its role on their response to lipopolysaccharide (LPS) were studied by using the murine TH2.52 B-1 cell line and peritoneal B-1 cells. TH2.52 cells with the B-1 phenotype were found to express membrane-bound CD14. Furthermore, CD14 was expressed on physiological peritoneal CD5+ B-1 cells. The stimulation of CD14-expressing TH2.52 cells with a low concentration of LPS resulted in the activation of nuclear factor (NF)-B and a mitogen-activated protein kinase (MAPK). The LPS-induced NF-B and MAPK activation was markedly inhibited by anti-CD14 antibody. These results suggest that B-1 cells may respond to LPS via membrane-bound CD14.

Mouse B1 cell line responds to lipopolysaccharide via membrane-bound CD14.

The role of membrane-bound CD14 in the response of mouse B1 cell lines to lipopolysaccharide (LPS) was studied. The surface profile of mouse TH2.52 B cells was positive for CD5, IgM, B220, CD11b and F4/80, suggesting that TH2.52 cells carried the typical phenotype of B1 cells. Furthermore, TH2.52 B1 cells were found to express membrane-bound CD14, which plays a critical role in LPS recognition. TH2.52 B1 cells responded to a very low concentration of LPS and exhibited: (i) augmentation of DNA synthesis; (ii) activation of nuclear factor (NF)-kappaB; and (iii) phosphorylation of extracellular signal regulated kinase 1/2 (Erk1/2). They were markedly inhibited by anti-CD14 antibody. Therefore, the expression of membrane-bound CD14 was suggested to provide high sensitivity to LPS for TH2.52 B1 cells.

Flavonoids protect mice from two types of lethal shock induced by endotoxin.

The protective effect of flavonoids on two types of lethal endotoxic shock was studied. A lethal endotoxic shock was induced by administration of lipopolysaccharide (LPS) into D-galactosamine (D-GalN)-sensitized mice and another one was done by administration of a high dose of LPS into normal mice. Pretreatment with a series of flavonoids protected mice from two types of endotoxin lethality. Flavonoid pretreatment reduced the serum tumor necrosis factor-alpha (TNF-alpha) level in mice injected with D-GalN and LPS, but not in mice injected with a high dose of LPS. TNF-alpha-induced lethal shock in D-GalN-sensitized mice was also protected by pretreatment with flavonoids, suggesting that flavonoids augmented the resistance to TNF-alpha lethality. On the other hand, flavonoids reduced the plasma level of lipid peroxides in mice injected with a high dose of LPS, but not in D-GalN-sensitized mice. Taken together, these results indicated that flavonoids might protect mice from two types of endotoxin lethality. The protective mechanism of flavonoids in each endotoxin lethality is discussed.

Inhibition of p38 mitogen-activated protein kinase augments lipopolysaccharide-induced cell proliferation in CD14-expressing Chinese hamster ovary cells.

CD14-expressing Chinese hamster ovary (CD14-CHO) cells, established by transfection of human CD14 DNA, acquired high responsiveness to lipopolysaccharide (LPS) through membrane-bound CD14 expression. LPS induced DNA synthesis and activated a series of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase 1/2 (Erk1/2), p38, and c-Jun N-terminal kinase/stress-activated protein kinase, in CD14-CHO cells but not in mock-transfected CHO cells. Anti-CD14 antibody completely abrogated both LPS-induced DNA synthesis and LPS-induced phosphorylation of those MAP kinases, suggesting a critical role of membrane-bound CD14 in LPS signaling. A p38 MAP kinase inhibitor, SB203580, markedly augmented LPS-induced DNA synthesis in CD14-CHO cells, whereas an Erk1/2 inhibitor, PD98059, had no affect. On the other hand, SB203580 exhibited no effect on epidermal growth factor-induced DNA synthesis in CD14-CHO cells, although PD98059 inhibited it significantly. The activation and inactivation of p38 MAP kinase with dominant negative and dominant positive mutants also suggested the participation of p38 MAP kinase in LPS-induced DNA synthesis. It was therefore suggested that the activation of p38 MAP kinase can negatively regulate LPS-induced cell proliferation in CD14-CHO cells.

Inhibition of caspase 3 abrogates lipopolysaccharide-induced nitric oxide production by preventing activation of NF-kappaB and c-Jun NH2-terminal kinase/stress-activated protein kinase in RAW 264.7 murine macrophage cells.

The effect of caspase inhibitors on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 267.4 murine macrophage cells was investigated. Pretreatment of RAW cells with a broad caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), resulted in a striking reduction in LPS-induced NO production. Z-VAD-FMK inhibited LPS-induced NF-kappaB activation. Furthermore, it blocked phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not that of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases. Similarly, a caspase 3-specific inhibitor, Z-Asp-Glu-Val-Asp-fluoromethylketone, inhibited NO production, NF-kappaB activation, and JNK/SAPK phosphorylation in LPS-stimulated RAW cells. The attenuated NO production was due to inhibition of the expression of an inducible-type NO synthase (iNOS). The overexpression of the dominant negative mutant of JNK/SAPK and the addition of a JNK/SAPK inhibitor blocked iNOS expression but did not block LPS-induced caspase 3 activation. It was therefore suggested that the inhibition of caspase 3 might abrogate LPS-induced NO production by preventing the activation of NF-kappaB and JNK/SAPK. The caspase family, especially caspase 3, is likely to play an important role in the signal transduction for iNOS-mediated NO production in LPS-stimulated mouse macrophages.

Production of experimental autoimmune sialadenitis in mice immunized with homologous salivary gland extract and Klebsiella O3 lipopolysaccharide.

An experimental murine model for autoimmune sialadenitis was produced by repeated immunization of homologous salivary gland extract together with Klebsiella O3 lipopolysaccharides as an immunological adjuvant. The cell infiltration was observed in the salivary glands of mice immunized more than twice. Inflammatory cells consisting mainly of CD4+ T cells and CD8+ T cells accumulated at the perivascular regions. There was hyperplasia and enlargement of ductal epithelial cells in the secretory acinar units in salivary glands of repeatedly immunized mice. The repeated immunization developed delayed-type hypersensitivity and autoantibody production to the homologous salivary gland extract. The immunohistochemical analysis showed positive staining on the cuboidal cells in the intercalated ducts, and the columnar pseudostratified cells in the striated ducts. Organ-specific antigens with molecular weights ranging from 20 to 90 kDa were recognized by the sera from immunized mice. Therefore, it was suggested that the sialadenitis was produced by the autoimmune mechanism and might be a new experimental model for characterization of the pathogenesis of autoimmune sialadenitis.