[Determination of seven perfluoroalkyl and polyfluoroalkyl substances in serum of pregnant women and evaluation of neonatal neurobehavior based on high performance liquid chromatography-tandem mass spectrometry].

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively used as synthetic fluorine-containing compounds in various consumer products, including surfactants, cookware, lubricants, clothing, and food packaging, since the 1950s. Evidence has shown that PFASs cross the placental barrier and interfere with fetal thyroid hormone homeostasis, which is crucial for fetal growth and neurobehavioral development in children aged 2-9 years. However, no epidemiological data on the association between prenatal PFAS exposure and neonatal neurobehavioral development are available. In this study, we explored the association between prenatal PFAS exposure and neonatal neurobehavioral development based on the Ezhou cohort study. Blood samples (10 mL) were collected during the third trimester of pregnancy (28-36 weeks) at the Ezhou maternal and child health hospital. The blood specimens were centrifuged at 4000 r/min for 15 min immediately after collection, separated, stored at -80 ℃. The samples were analyzed for seven PFASs, namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonamide (PFOSA). The PFASs were separated using a C18 column (100 mm×2.1 mm, 1.7 µm) at an oven temperature of 40 ℃, injection volume of 10 µL, and flow rate of 0.4 mL/min via gradient elution with methanol and ammonium acetate aqueous solution. The instrument was operated in negative electrospray ionization mode with multiple reaction monitoring. The correlation coefficients (r2), limits of detection (LODs) and quantification (LOQs), and spiked recoveries of the seven PFASs were 0.993-0.999, 0.006-0.020 ng/mL, 0.020-0.066 ng/mL, and 84.6%-116.8%, respectively. Neonatal behavioral neurological assessment (NBNA) was used to evaluate newborn cognitive development 72 h after birth; this tool consisted of five clusters, including behavior (six items), passive muscle tone (four items), active muscle tone (four items), primitive reflexes (three items), and general assessment (three items). Each item was rated on a three-point scale (0, 1, or 2), with the 20 items having a maximum score of 40. A total of 379 mother-newborn pairs were included in the analysis. The PFASs with the highest exposure levels was PFOA, with median levels of 19.4 ng/mL. Linear regression models were used to test the effects of ln-converted PFAS levels in newborns. After adjusting for confounding factors, the linear regression model showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(ß(95% CI): 0.36(-0.64, 0.08)) and general assessment(ß(95% CI): 0.34(-0.61, 0.07)) in all newborns. Furthermore, PFNA exposure was associated with decreased passive muscle tone(ß(95% CI): 0.38(-0.74, 0.01)) and total NBNA(ß(95% CI): 0.37(-0.68, 0.06)). PFDA exposure was associated with decreased behavior(ß(95% CI): 0.28(-0.54, 0.01)), while PFHxS exposure was associated with elevated total NBNA(ß(95% CI): 0.27(0.05-0.48)). Gender stratification analysis showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(ß(95% CI): 0.54(-0.73, 0.35)) and general assessment(ß(95% CI): 0.50(-0.88, 0.13)), PFNA exposure during pregnancy was associated with decreased passive muscle tone(ß(95% CI): 0.67(-1.2, 0.14)) and total NBNA(ß(95% CI): 0.45(-0.91, 0.01)), PFDA exposure during pregnancy was associated with decreased behavior(ß(95% CI): 0.44(-0.71, 0.17)), PFHxS exposure was associated with elevated total NBNA(ß(95% CI): 0.41(0.02-0.80)) in male newborns, and PFOA exposure was associated with decreased general assessment(ß(95% CI): -0.27(-0.51, 0.02)), and PFDA exposure was associated with elevated behavior(ß(95% CI): 0.46(0.40-0.52)) in female newborns. The proposed method separates and detects various PFASs without the need for cumbersome pretreatment processes, and has the advantages of low LODs, satisfactory recoveries, and accurate precision. Thus, it allows for the simultaneous analysis of trace PFASs in microserum samples from pregnant women. Our results also showed that prenatal PFAS exposure can lead to neurobehavioral disorders in offspring, with male newborns showing greater sensitivity than female newborns.

Pulmonary alveolar proteinosis complicated with tuberculosis: A case report.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of phospholipoproteinaceous material in the alveoli. Cases of PAP complicated with tuberculosis are much more complex and have rarely been well recorded. CASE SUMMARY: We describe a 21-year-old Han Chinese patient with suspicious lung infection associated with mild restrictive ventilatory dysfunction and diffusion reduction. High resolution computed tomography revealed a "crazy-paving" appearance and multiple pulmonary miliary nodules around the bronchi. Bronchoalveolar lavage demonstrated a small amount of periodic acid-Schiff positive proteinaceous materials. A serological test for the presence of a Mycobacterium tuberculosis antibody and an interferon-gamma release assay were both positive. The patient received a standard course of first-line anti-tuberculosis treatment after diagnostic bronchoalveolar lavage. To date, clinical remission has been achieved and maintained for five years. CONCLUSION: In summary, the diagnosis of PAP complicated with tuberculosis was supported by a combination of clinical manifestations, imaging, pulmonary function, laboratory examinations, bronchoalveolar lavage, etc. This case highlighted that diagnostic bronchoalveolar lavage in combination with anti-tuberculosis treatment is a safe and effective option for mild PAP patients with tuberculosis.

Is the delivery mode a critical factor for the microbial communities in the meconium?

BACKGROUND: Mothers are the primary source of bacteria for newborns, but it is unclear whether mother-to-newborn transmission occurs prior to, during or after birth. Similarly, the effect of the delivery mode on neonatal microorganisms has been the focus of controversy. METHODS: Healthy maternal and neonatal pairs that underwent vaginal birth and caesarean section were enrolled in this study. Meconium, placenta, membrane and amniotic fluid samples for newborns and vaginal, rectal and oral samples for mothers were collected. All samples were amplified and sequenced by a 16S rRNA gene primer set targeting bacteria and archaea. FINDINGS: A total of 550 samples from 36 mother-neonate pairs with vaginal births and 42 mother-neonate pairs with caesarean sections were included in this study. The negative controls showed that the data analysis in this study was not affected by contamination. There was a high diversity of microbial communities in the pregnancy environment of the foetus. Meconium samples could be divided into three distinct types that were not influenced by the delivery method. INTERPRETATION: The distribution patterns of bacterial communities in the meconium, placenta, and foetal membranes were highly similar and had nothing to do with the mode of delivery. For approximately half of the placental microorganisms, the same sequence could be found in the vaginal, rectal, and oral samples of the mother.

Novel mutations in the lipase H gene lead to secretion defects of LIPH in Chinese patients with autosomal recessive woolly hair/hypotrichosis (ARWH/HT).

Autosomal recessive woolly hair/hypotrichosis (ARWH/HT: OMIM #278150/604379) is a rare hereditary hair disease characterized by tightly curled hair at birth which can lead to sparse hair later in life. The mutations in both LIPH and LPAR6/P2RY5 are responsible for autosomal recessive woolly hair with or without hypotrichosis (ARWH/HT). To conduct clinical and genetic investigations in four patients from three unrelated Chinese Han families with ARWH/HT, we performed mutation screening of LIPH and LPAR6/P2RY5 gene and identified four mutations in LIPH: c.454G>A, c.614A>G, c.736T>A, c.742C>A. c.736T>A and c.742C>A mutations were reported in previous studies, and c.454G>A, c.614A>G were identified for the first time. We carried out functional studies of the two mutants with c.454G>A (p.Gly152Arg, G152R) or c.614A>G (p.His205Arg, H205R). Interestingly, both of them lead to secretion defects of LIPH, which are involved in the pathogenesis of ARWH/HT.

Simultaneous heart valve replacement surgery and abdominal subtotal hysterectomy: case report.

A middle-aged woman with rheumatic heart disease, mitral valve prolapse and incompletely closed mitral valve medium, patent foramen ovale, merge multiple uterine fibroids, and moderate blood loss anemia underwent mitral valve replacement surgery with total abdominal hysterectomy under general anesthesia and cardiopulmonary bypass condition. The surgery was successful, and postoperative bleeding, blood clots, heart failure, and other related complications did not occur. Heart valve replacement surgery with the surgical treatment of uterine fibroids effectively improves the safety of surgical treatment for patients as well as reduces the patient's medical expenses and risk of secondary surgery and trauma.

Mutation detection of type II hair cortex keratin gene KRT86 in a Chinese Han family with congenital monilethrix.

BACKGROUND: Monilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules. In this study, we collected a Han monilethrix family to detect the mutations in patients and investigated the correlation between the genotype and phenotype of monilethrix. METHODS: In this study, we identified a Chinese family with monilethrix through light microscopic and scanning electron microscopic (SEM) examination. Genomic DNA from peripheral blood samples was prepared. DNA samples from controls and monilethrix patients were subject to polymerase chain reaction (PCR) amplification. Two pairs of primers were used to amplify the seventh exon of KRT86. Mutation screening of the PCR products was detected using direct sequencing. RESULTS: Light microscopic examination showed a regular alternate enlargement and narrow area. SEM examination showed that part of the cuticle of the nodules shed and disappeared gradually in the narrow area with granular protrusions on the surface similar to the erosion-like structure. Parallel longitudinal ridge and groovepattern appeared, and the ridges varied in width, like dead wood. A heterozygous transversion mutation c.1204G > A (p.E402K) in the seventh exon of KRT86 was identified in both patients. CONCLUSIONS: The mutation of extron 7 of KRT86 identified plays a major role in the pathogenesis of this pedigree with monilethrix, and is a mutation hot spot of KRT86. Further research is needed to explore the relationship between the phenotype and the mutation of the type II hair keratin gene KRT86 of monilethrix.

Novel deletion mutation of TRPS1 gene in a Chinese patient of trichorhinophalangeal syndrome type I.

Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant disorder. Deletion or mutation of the TRPS1 gene leads to the tricho-rhino-phalangeal syndromes type I or type III. In this article, we describe a Chinese patient affected with type I TRPS and showing prominent pilar, rhinal and phalangeal abnormalities. Mutational screening and sequence analysis of TRPS1 gene revealed a previously unidentified four-base-pair deletion of nucleotides 1783-1786 (c.1783_1786delACTT). The mutation causes a frame shift after codon 593, introducing a premature stop codon after 637 residues in the gene sequence. This deletion is an unquestionable loss-of-function mutation, deleting all the functionally important parts of the protein. Our novel discovery indicates that sparse hair and metacarpal defects of tricho-rhino-phalangeal syndromes in this patient are due to this TRPS1 mutation. And this data further supports the critical role of TRPS1 gene in hair and partial skeleton morphogenesis.

A new c.1845A→T of oncostatin M receptor-ß mutation and slightly enhanced oncostatin M receptor-ß expression in a Chinese family with primary localized cutaneous amyloidosis.

Primary localized cutaneous amyloidosis (PLCA) is a chronic itching skin disease with amyloid material deposited in the upper dermis. PLCA is more common in Southeast Asia and South America, where up to 10% of cases may be familial. Mutations of OSMR or IL31RA have been identified in PLCA. Here we detected a new OSMR mutation in a lichenoid PLCA family from north China. This is the first report of PLCA with gene mutation on the Chinese mainland. A heterozygous 1845A→T was found in exon 13 of the proband, causing p.Lys615Asn substitution, which was not found in screening 100 ethnically matched healthy controls. The particular mutated amino acid is well conserved throughout various evolutionary lineages, located within the second fibronectin III-like domain of oncostatin M receptor ß subunit (OSMRß), and in close vicinity to a previously reported mutation, p.Gly618Ala. Immunohistochemistry showed slightly enhanced OSMRß expression in the lesion of the proband. This study extends the knowledge of PLCA gene mutation and further supports the pathogenic role of OSMRß in PLCA.

Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model.

BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease, which is closely associated with cigarette smoking. However, the signal transduction pathway from the cell surface to the nucleus through which cigarette smoke causes upregulation of mucin gene expression is not well known. This study was designed to investigate the role of extracellular signal-regulated Kinase 1/2 (ERK 1/2) in airway mucus hypersecretion induced by cigarette smoke in rats. METHODS: A rat model of airway mucus hypersecretion was induced by exposure to cigarette smoke for 4 weeks.Rats exposed to inhalation of cigarette smoke or normal saline were given an intraperitoneal injection of U0126, a specific MEK1 kinase inhibitor, at doses of 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg for 14 days. Expression of MUC5AC mRNA and protein, ERK 1/2 and phosphorylated-ERK 1/2 (p-ERK 1/2) were detected by RT-PCR, immunohistochemistry and Western blotting. RESULTS: Cigarette smoke significantly increased airway goblet cells metaplasia, induced the overexpression of MUC5AC mRNA and protein in bronchial epithelia, and increased the ratio of p-ERK 1/2 and ERK 1/2. U0126 significantly attentuated the expression of MUC5AC mRNA and protein induced by cigarette smoke (P < 0.05). Moreover, there was a significant positive correlation between the ratio of p-ERK1/2 to ERK1/2 and the expression of MUC5AC mRNA and protein (P < 0.05). CONCLUSIONS: Inhibition of ERK 1/2 by U0126 decreased the ratio of p-ERK 1/2 to ERK 1/2 and expression of MUC5AC mRNA and protein. ERK 1/2 may play an essential role in cigarette smoke-induced mucus hypersecretion in vivo.

Manufacture of cellulose nanocrystals by cation exchange resin-catalyzed hydrolysis of cellulose.

Cellulose nanocrystals (CNC) were prepared from microcrystalline cellulose (MCC) by hydrolysis with cation exchange resin (NKC-9) or 64% sulfuric acid. The cation exchange resin hydrolysis parameters were optimized by using the Box-Behnken design and response surface methodology. An optimum yield (50.04%) was achieved at a ratio of resin to MCC (w/w) of 10, a temperature of 48 °C and a reaction time of 189 min. Electron microscopy (EM) showed that the diameter of CNCs was about 10-40 nm, and the length was 100-400 nm. Regular short rod-like CNCs were obtained by sulfuric acid hydrolysis, while long and thin crystals of cellulose were obtained with the cation exchange resin. X-ray diffraction (XRD) showed that, compared with MCC, the crystallinity of H2SO4-CNC and resin-CNC increased from 72.25% to 77.29% and 84.26%, respectively. The research shows that cation exchange resin-catalyzed hydrolysis of cellulose could be an excellent method for manufacturing of CNC in an environmental-friendly way.

[Clinical application study of modified Moore classification in lower cervical spine injuries].

OBJECTIVE: To analyze the clinical application of modified Moore classification in lower cervical spine injuries. METHODS: Modified Moore classification was applied in the morphologic description of 200 patients (including 165 males, 35 females,age ranging from 19 to 88 years,with an average age of 52 years) with lower cervical spine injuries from August 2006 to March 2010, cervical spine injury severity score (quantification of stability) in combination with yes/no neurological injury status to classify their clinical diagnosis and management. The treatment was selected according to the fracture type, stability, compression injury of spinal cord or nerve roots, stability of ligamentous injury and other reference factors. According to the ASIA score, 130 cases with injury of spinal cord or nerve root (i.e. 6 cases in Grade A,13 cases in Grade B,43 cases in Grade C, 68 cases in Grade D); and 70 cases with no injury of spinal cord or nerve root. The ASIA score was applied in the evaluation of curative effect in cases with injury of spinal cord or nerve root. Radiodiagnostics was used to observe sequential measurement of cervical vertebrae and height in cases without spinal cord or nerve root injuries. RESULTS: The cervical spine injury distribution is that 35 cases of anterior, left, right lateral and posterior column injury; 33 cases of anterior column injury; 90 cases of anterior and posterior column injury; 5 cases of anterior, left lateral and posterior column injury; 3 cases of anterior, right lateral and posterior column injuries; 3 cases of anterior, left and right lateral column injuries; 2 cases of anterior and right lateral column injuries; 5 cases of anterior and left lateral column injury; 12 cases of posterior column injury; 7 cases of left lateral column injury; 5 cases of right lateral column injury. Surgery operation was given in 98 patients out of 200 cases. Non-surgical treatment was given to 102 patients (including 39 patients who are qualified to receive operation, but patient's relative required non -surgical treatment). Three cases of complete injury of spinal cord showed no recovery of the spinal cord function after operation, no change on the ASIA score, but pain and numbness of limb relieved slightly. Three non-surgical treatment cases showed no change after the treatment. Cases of incomplete injury of spinal cord showed certain recovery on spinal cord function after operation, and the ASIA score was raised 1.2 grades averagely. The ASIA score of cases of incomplete injury of spinal cord after non-surgical treatment was raised 0.3 grades averagely. The alignment and height of cervical vertebras were normal on post-operative radiodiagnostics in patients without injury of spinal cord or nerve root. CONCLUSION: According to modified Moore classification, when the stability quantification score is higher than or equal to 4, it indicated that the cervical vertebras are instability in lower cervical spine injuries. Surgery operation is required in higher score and less stability cases. Cases associated with neurological injury must receive surgery operation. Cases with stability quantification score equals to 3 and neurological injury should also receive surgery operation in general. Surgery operation is not required in cases of stability quantification equal to 3 and without neurological injury,or cases of stability quantification score lower than 3. Applying modified Moore classification in the treatment of lower cervical spine injuries is beneficial for the clinical standardization, diagnosis and treatment and receives satisfactory therapeutic effects.

[Preparation and spectrum properties of cellulose nanoparticles].

Manipulating cellulose molecules in nanosize range to create excellent nano materials is the frontier of cellulose science. Cellulose nanoparticles, a kind of renewable biomaterial, have become the research focus home and aboard. It is of great importance to develop a simple, green, low energy-consuming, rapid and efficient method to prepare cellulose nanoparticles. In the present paper, cellulose nanoparticles (CNP) which enjoy good dispersity and nanosize were prepared by alkaline hydrolysis in a simple and feasible way, with microcrystalline cellulose (MCC) as the raw material. Moreover, the size and morphology, crystal structure and spectrum properties of the cellulose nanoparticles were analyzed by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FTIR). TEM images demonstrate that the prepared samples are in quasi-sphere shapes with good dispersity and with size about 20-40 nm. The SEM images of the samples show that the purified cellulose nanoparticles can be obtained after dialysis treatment to remove salt particles. The XRD results show that the microcrystalline cellulose and cellulose nanoparticles almost have the same diffraction peaks in cellulose I crystal form. Because of the damage of amorphous region of MCC by alkaline hydrolysis, the crystallinity of produced samples increases by up to 79.71%. The grain size was calculated with Scherrer's formula, and the average size is about 3-6 nm. Furthermore, the FTIR spectra suggest that the characteristic peaks on the graphs of cellulose nanoparticles have no significant change compared to natural cellulose, which indicates that the sample remains as the basic chemical groups of cellulose. The results show that preparing cellulose nanoparticles (CNP) by alkaline hydrolysis enjoys the ease to operate and can produce high yield, and therefore the study offers a new approach to obtaining cellulose nanoparticles with nanosize and good dispersion.

Effectiveness and safety of bevacizumab for unresectable non-small-cell lung cancer: a meta-analysis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts for more than 85% of all cases of lung cancer. The 5-year survival of patients presenting with advanced stage NSCLC is less than 15%, indicating that additional treatment options are needed. Bevacizumab is a recombinant humanized version of the murine anti-human vascular endothelial growth factor (VEGF) monoclonal antibody with a high binding specificity for VEGF. OBJECTIVE: The aim of this meta-analysis was to evaluate the effectiveness and safety of bevacizumab in patients with unresectable non-small-cell lung cancer (NSCLC) on the basis of evidence-based methodology. METHODS: The electronic database PubMed was searched to identify randomized, controlled trials (RCTs) of bevacizumab for the treatment of unresectable NSCLC. Other databases such as the Cochrane Library Trials Register, the WHO Trial Registration, the National Cancer Institute, ClinicalTrials.gov, the European Organization for Research and Treatment of Cancer, the Southwest Oncology Group, the Eastern Cooperative Oncology Group, the European Society of Clinical Oncology and the American Society of Clinical Oncology were also searched. The meta-analysis was performed using Reviewer Manager Version 5.0 software provided by the Cochrane Collaboration. Outcome measures were overall survival rates, progression-free survival, tumour response rate, incidence of severe adverse events (SAEs) and treatment-related death. RESULTS: Four eligible studies that included 2101 patients were found; in these studies, bevacizumab was administered to 1237 patients. Neither high-dose (15 mg/kg) nor low-dose (7.5 mg/kg) bevacizumab increased 1-year overall survival rates compared with patients not treated with bevacizumab. However, high-dose bevacizumab, rather than low-dose, increased 2-year overall survival rate (risk ratio [RR] = 1.24; 95% confidence interval [CI] 1.04, 1.49) and tumour response rate (RR = 1.69; 95% CI 1.21, 2.35) compared with patients not treated with bevacizumab. Progression-free survival was also significantly improved in both the low- (hazard ratio [HR] = 0.76; 95% CI 0.64, 0.90) and high-dose groups (HR = 0.73; 95% CI 0.65, 0.81). There was a clear and significant increase in the rate of treatment-related death in the high-dose group (RR = 2.07; 95% CI 1.19, 3.59) compared with patients not treated with bevacizumab. No significant differences were noted in the rate of treatment-related death in the low-dose group or in the incidences of SAE in the low- or high-dose groups compared with patients not treated with bevacizumab. Neutropenia was easily induced in both the low- and high-dose bevacizumab groups. Patients who received high-dose bevacizumab tended to experience hypertension, neutropenia, haemoptysis, rash and headache more frequently than patients not treated with bevacizumab. CONCLUSIONS: Low-dose bevacizumab may significantly improve progression-free survival in patients with unresectable NSCLC, whereas high-dose bevacizumab may increase 2-year overall survival rates, prolong progression-free survival and improve tumour response rate but at the cost of higher treatment-related death. Larger well designed RCTs should be carried out in the future to clarify the role of bevacizumab in the treatment of NSCLC.

Role of BMP3 in progression of gastric carcinoma in Chinese people.

AIM: To investigate the relation between gastric cancer and microsatellite instability (MSI), loss of heterozygosity (LOH) and promoter region methylation. METHODS: Fifty primary gastric carcinoma specimens were collected from patients with no family history of cancer. In addition, normal tissues were also collected from patients as controls. DNA was extracted by polymerase chain reaction for single-strand conformation polymorphism, bisulfite DNA sequencing, and methylation-specific band analysis. RESULTS: The positive rate for MSI and LOH in gastric carcinoma was 16% and 20%, respectively. According to the tumor, node and metastasis staging system, the LOH frequency was higher in gastric carcinoma at stages III and IV than in gastric carcinoma at stages I and II (P = 0.01), which was also significantly correlated with lymph node metastasis and clinico- pathological characteristics of gastric carcinoma. Methylation of bone morphogenetic protein 3 (BMP3) gene promoter was detected in 64.44% of gastric carcinoma tissue samples. However, no statistical significance was observed between promoter region methylation and carcinoma differentiation. Interestingly, the BMP3 gene methylation rate was 71.05% and 28.58%, respectively, in MSI positive and negative cases (P = 0.031), suggesting that BMP3 genetic instability and promoter methylation are initiated during gastric carcinogenesis. LOH was detected mostly in the late stages of gastric carcinoma, indicating that gastric carcinoma at late stages has a higher infiltration and a poorer prognosis. CONCLUSION: Promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people.

[A study on the haplotype of the solute carrier family 11 member 1 gene in Tibetan patients with pulmonary tuberculosis in China].

OBJECTIVE: To investigate the association of the haplotype of the solute carrier family 11 member 1 (SLC11A1) gene with susceptibility to pulmonary tuberculosis in Tibetans. METHODS: Four polymorphisms of the SLC11A1 gene [5' (GT)n, INT4, D53N, and 3' UTR] were investigated by denaturalization high performance liquid chromatography and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 140 patients (the patient group) and 139 PPD-positive healthy controls (the control group) of the Tibetan nationality from June 2004 until January 2005. The relationship between the haplotype and susceptibility to pulmonary tuberculosis in these patients was studied by chi2 test, and the linkage disequilibrium as well as the haplotype were analyzed by the SHESIS software. RESULTS: The haplotype frequencies of 5'(GT)9/INT4 G, 3'UTR TGTG/D543N G, 3'UTR TGTG del/D543N A were 64.8% (181/280), 76.6% (215/280), 12.0% (34/280) among the patients and 78.1% (217/276), 84.4% (235/276), 6.4% (18/276) among the controls. 5' (GT)9/INT4 G, 3'UTR TGTG/D543N G haplotypes rendered a lower risk (chi2 = 11.026, P<0.01, chi2 = 6.547, P<0.05, respectively), but 3'UTR TGTG del/D543N A haplotype a higher risk (chi2 = 6.547, P<0.05) for tuberculosis. CONCLUSIONS: 5' (GT)9/INT4 G, 3'UTR TGTG/D543N G and 3'UTR TGTG del/D543N A haplotypes of the SLC11A1 gene may be associated with the susceptibility of the Tibetan population to pulmonary tuberculosis.

Short report: case of gnathostomiasis in Beijing, China.

A 59-year-old woman sought treatment of for creeping eruption and erythematous plaques associated with high fever and systemic symptoms. She had a history of eating undercooked freshwater fish raised in Beijing 10 days before admission and reported no travel during the previous year. Blood examination showed eosinophila and ultrasonography detected multiple hypoechoic areas in the liver and spleen. Western blot test detected specific antibodies to the larvae of Gnathostoma spinigerum. Cutaneous and visceral larva migrations associated with G. spinigerum were diagnosed. Twenty-three cases in 12 provinces have been reported in the Chinese literature but none have been reported in English.

Mycophenolate mofetil and triptolide alleviating airway inflammation in asthmatic model mice partly by inhibiting bone marrow eosinophilopoiesis.

The bone marrow eosinophilopoiesis makes a major contribution to the chronic airway inflammation in asthmatic animals and patients. Some anti-asthmatic medicines alleviated the asthmatic airway inflammation by inhibiting the bone marrow eosinophilopoiesis. Immunosuppressive agents have been commonly used in patients with glucocorticoid refractory asthma and have been proved to be effective. However, the research on the effect of the immunosuppressive agents on the bone marrow eosinophilopoiesis has seldom been reported. The purpose of the study was to explore the effect of mycophenolate mofetil (MMF) and triptolide (TP) on the bone marrow eosinophilopoiesis and to further investigate the mechanisms of the immunosuppressive agents involved in the anti-asthmatic effect. Balb/c mice were sensitized and challenged by OVA to establish the asthmatic model, and respectively administered orally with sterile saline, MMF, and TP once daily for 2 weeks. Airway inflammation, and inflammatory mediators IL-5 and eotaxin in the peripheral blood and bone marrow were measured by histology and ELISA. Immunocytochemistry combined with in situ hybridization technique and Western blot analysis was performed to estimate the amount of CD34+ IL-5R mRNA+ cells and IL-5R expression in the bone marrow. The count of new produced eosinophils in the bone marrow was detected by anti-BrdU immunocytochemistry. We found that MMF and TP attenuated OVA-induced eosinophil (EOS) recruitment in bronchoalveolar lavage fluid (BALF), inflammatory mediator expression of IL-5 and eotaxin in the peripheral blood, inflammatory cells expressing eotaxin in the lung tissues and the number of new produced EOS in the bone marrow. Also, MMF abated the migration of CD34+ cells from the bone marrow to the peripheral blood, which was associated with a decreased eotaxin expression in the bone marrow and a decreased CCR3 expression on bone marrow cells. While, MMF or TP failed to decrease the amount of CD34+ IL-5R mRNA+ cells (EOS progenitors), and IL-5R expression in the bone marrow of asthmatic model mice. These results demonstrated that MMF and TP reduce the eosinophilopoiesis of the bone marrow; this is associated with a decrease of IL-5 produced by T cells, which contribute to alleviate the allergic airway inflammation in asthma. In addition, MMF decreased the CD34+ cells migration from the bone marrow to the peripheral blood by the reduction of the level of eotaxin in the bone marrow and the expression of CCR3 on the bone marrow cells.

Increased expression of human calcium-activated chloride channel 1 is correlated with mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC(1)) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC(1) and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC(1), MUC5AC and mucus in bronchial tissues were examined. METHODS: Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC(1), MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively. RESULTS: Compared with the control group, the stronger expressions of CaCC(1) were further detected throughout the bronchial tissues from patients with COPD (P < 0.01). Furthermore, the stronger expressions of the CaCC(1) mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P < 0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P < 0.01). Expression levels of the CaCC(1) mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) data, FEV(1)% predicted data, V(50)% predicted data, V(25)% predicted data (r = -0.43, r = -0.43, r = -0.35, r = -0.36, P < 0.01, P < 0.01, P < 0.05, P < 0.05). While the expression levels of the CaCC(1) mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r = 0.39, r = 0.46, P < 0.05, P < 0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV(1)/FVC data (P = 0.01), FEV(1)% pred data (P = 0.01), V(50)% predicted data, V(25)% predicted data (r = -0.53, r = -0.53, r = -0.48, r = -0.43, P < 0.01, P < 0.01, P < 0.01, P < 0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P < 0.05), and the correlation coefficients were 0.43. CONCLUSION: These results suggest that the stronger gene expression of CaCC(1) exists, complicated with mucus overproduction in the airway of Chinese patients with COPD.