Antisense Oligonucleotides Targeting Jagged 1 Reduce House Dust Mite-induced Goblet Cell Metaplasia in the Adult Murine Lung.

Goblet cell metaplasia, excessive mucus production, and inadequate mucus clearance accompany and exacerbate multiple chronic respiratory disorders, such as asthma and chronic obstructive pulmonary disease. Notch signaling plays a central role in controlling the fate of multiple cell types in the lung, including goblet cells. In the present study, we explored the therapeutic potential of modulating the Notch pathway in the adult murine lung using chemically modified antisense oligonucleotides (ASOs). To this end, we designed and characterized ASOs targeting the Notch receptors Notch1, Notch2, and Notch3 and the Notch ligands Jag1 (Jagged 1) and Jag2 (Jagged 2). Pulmonary delivery of ASOs in healthy mice or mice exposed to house dust mite, a commonly used mouse model of asthma, resulted in a significant reduction of the respective mRNAs in the lung. Furthermore, ASO-mediated knockdown of Jag1 or Notch2 in the lungs of healthy adult mice led to the downregulation of the club cell marker Scgb1a1 and the concomitant upregulation of the ciliated cell marker FoxJ1 (forkhead box J1). Similarly, ASO-mediated knockdown of Jag1 or Notch2 in the house dust mite disease model led to reduced goblet cell metaplasia and decreased mucus production. Because goblet cell metaplasia and excessive mucus secretion are a common basis for many lung pathologies, we propose that ASO-mediated inhibition of JAG1 could provide a novel therapeutic path for the treatment of multiple chronic respiratory diseases.

Orbital sparganosis in an 8-year boy: a case report.

BACKGROUND: Sparganosis is one of the neglected but important food-borne parasitic zoonoses, with higher prevalence in Asian countries. The infection is commonly located in the subcutaneous tissue, brain, breast, and lung, but fewer reported infections involve the eye. Because the majority of patients with sparganosis are adults, it is likely to be missed in children. CASE PRESENTATION: An 8-year-old boy presented to our clinic complaining of a painless ocular mass in his right eye for 1 month. The boy had a history of eating frogs and frog poultice applications to his eyelids. The patient was checked for an elliptical mass near the medial wall of the right eye. Serodiagnosis testing was positive in an enzyme-linked immunosorbent assay. During surgical operation on the patient, calcified parasite eggs and foreign body granulomatous reaction were found using histological examination. Due to early detection and surgery, the patient fully recovered with no damage to his eyesight. CONCLUSIONS: Although rare, ocular sparganosis should be suspected in a mass of the eye when there is a history of eating frogs and frog poultice applications on eyelids. Early surgical resection is important for a good prognosis.

Increasing occurrence of antimicrobial-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in China.

BACKGROUND: New hypervirulent variants of Klebsiella pneumoniae (hvKP) are emerging globally, most of which exhibit antimicrobial susceptibility. METHODS: A retrospective study was conducted in 88 patients with cultures positive for K. pneumoniae hospitalized in the Beijing You'an Hospital from April 2010 to June 2012. The clinical and molecular data of the hvKP isolates (defined as string test positive) were compared with those of the classic K. pneumoniae (cKP) isolates. RESULTS: Overall, 33.0% (29/88) of K. pneumoniae isolates were hvKP. Univariate analysis revealed the following risk factors for hvKP: virulence gene rmpA (odds ratio [OR], 16.92 [95% confidence interval {CI}, 4.842-59.145]), capsule antigens K1 (OR, 3.355 [95% CI, 1.153-9.768]) and K2 (OR, 9.280 [95% CI, 0.987-87.250]), alcoholic hepatitis (OR, 7.435 [95% CI, 1.397-39.572]), liver abscess (OR, 9.068 [95% CI, 1.747-47.061]), metastatic infection (OR, 2.752 [95% CI, 1.100-6.886]), community-acquired infection (OR, 10.432 [95% CI, 3.623-30.033]), sputum isolation (OR, 0.312 [95% CI, .095-1.021]), and HIV infection (<0.001 [not applicable]). Multivariate analysis implicated rmpA (OR, 17.398 [95% CI, 4.224-71.668]) and community-acquired infection (OR, 6.844 [95% CI, 1.905-24.585]) as independent risk factors. The proportion of hvKP isolates increased from April to December 2010, January to September 2011, and October 2011 to June 2012 (to 25.5%, 26.7%, and 54.5%, respectively). Resistance to 14 of 19 tested antimicrobials was found to be significantly greater in cKP compared to hvKP. Importantly, resistance to all the tested antimicrobials, except carbapenems and amikacin, was observed in a proportion of hvKP strains, 17% (5/29) of which expressed extended-spectrum ß-lactamase. Furthermore, antimicrobial resistance in hvKP strains increased over time. CONCLUSIONS: HvKP strains are being isolated from patients in China with increasing frequency and constitute an increasing proportion of K. pneumoniae strains, indicating an increasing propensity for the acquisition of antimicrobial resistance.

Isolation and Characterization of Pseudomonas aeruginosa Phages with a Broad Host Spectrum from Hospital Sewage Systems and Their Therapeutic Effect in a Mouse Model.

This study aimed to isolate and characterize phages as an alternative treatment of multidrug- or pan-drug-resistant Pseudomonas aeruginosa. Phage titers and bacterial densities correlated, with the phages disappearing after bacteria were eliminated. We isolated phages in filtered sewage water by a double-layered agar spot test. Fifty-eight P. aeruginosa strains were used to screen the host spectrum of the 14 phages isolated. Random amplification of polymorphic DNA-typing polymerase chain reaction was used to analyze the genomic homologies of the 58 host bacteria strains and four phages with a broad host spectrum. Transmission electron microscopy was used to observe the morphology of the four phages with a broad host spectrum. Mice with intraabdominal P. aeruginosa infection were used as an in vivo animal model to investigate the therapeutic effect of the selected phage. Four virulent phages with a broad host spectrum specific to P. aeruginosa strains were isolated. They were all double-stranded DNA viruses and belonged to four different genotypes. The test curve showed that phage I had the highest adsorption rate, the shortest latent period, and the largest burst size. The infected mouse model indicated that small doses of phage I could prevent the death of infected mice. Phage titers and bacterial densities correlated, with phages disappearing after bacteria were eliminated. Phage I was the most effective and promising treatment of drug-resistant P. aeruginosa.

In Vitro Activities of Aztreonam-Avibactam, Eravacycline, Cefoselis, and Other Comparators against Clinical Enterobacterales Isolates: a Multicenter Study in China, 2019.

Aztreonam-avibactam, eravacycline, and cefoselis are three novel antimicrobial agents for the treatment of serious infections caused by Gram-negative bacteria. We evaluated the in vitro activities of the above-mentioned three antimicrobial agents against clinical Enterobacterales isolates. A total of 1,202 Enterobacterales isolates, including 10 genera or species, were collected from 26 hospitals that cover seven regions of China. The susceptibilities of the 30 antimicrobial agents were interpreted based on the combination of U.S. Food and Drug Administration and Clinical and Laboratory Standards Institute guidelines. The results indicated that all Enterobacterales isolates showed high susceptibility to aztreonam-avibactam (98.25%), eravacycline (85.69%), and cefoselis (62.73%). The first two antimicrobial agents also demonstrated potent activities against multidrug-resistant and carbapenem-resistant Enterobacterales independent of antimicrobial resistance mechanisms. The rates of susceptibility to aztreonam-avibactam, eravacycline, and cefoselis were lowest in Morganella spp. (84.42%), Proteus spp. (33.65%), and Escherichia coli (40.14%), respectively. In general, the lower rates of susceptibility to eravacycline and cefoselis were in the older inpatient group. The strains isolated from urinary tract exhibited the lowest rate of susceptibility (78.97%) to eravacycline, and the lowest rate of susceptibility (45.83%) to cefoselis was observed in nervous system specimens. The strains isolated from intensive care unit (ICU) wards showed significantly reduced susceptibility to cefoselis compared with those isolated from non-ICU wards. The MIC values of aztreonam-avibactam and ceftazidime-avibactam have poor consistency (weighted kappa = 0.243), as did eravacycline and tigecycline (weighted kappa = 0.478). Cefoselis and cefepime showed highly similar activities against Enterobacterales (weighted kappa = 0.801). Our results support the clinical development of aztreonam-avibactam, eravacycline, and cefoselis to treat infections caused by Enterobacterales. IMPORTANCE Infections caused by multidrug-resistant (MDR) Enterobacterales, especially carbapenem-resistant Enterobacterales (CRE), have been a challenging clinical problem due to the limited therapeutic options. Therefore, the need to develop novel antimicrobial agents and evaluate their activities against Enterobacterales in vitro is urgent. Our results show that the novel antimicrobial agents aztreonam-avibactam and eravacycline retain activities against MDR and CRE isolates, including carbapenemase producers and non-carbapenemase producers. Further analysis combined with clinical information on the strains tested revealed that no significant differences were observed in susceptibility rates of strains with different demographic parameters to aztreonam-avibactam. Age, specimen source, and department were associated with the susceptibility of strains to eravacycline and cefoselis (P ≤ 0.01). Compared with ceftazidime-avibactam, aztreonam-avibactam has its advantages and limitations against Enterobacterales. The potent activity of eravacycline against Enterobacterales was higher than that of tigecycline. Cefoselis and cefepime showed a highly consistent activity against Enterobacterales.

Diagnostic value of alpha-fetoprotein, Lens culinaris agglutinin-reactive alpha-fetoprotein, and des-gamma-carboxyprothrombin in hepatitis B virus-related hepatocellular carcinoma.

OBJECTIVE: This study aimed to explore the use of different combinations of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) for the early diagnosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). METHODS: There were 167 subjects, including 100 with HCC and 67 with LC, who were enrolled into this study. Serum AFP, AFP-L3, and DCP levels were detected by chemiluminescent enzyme immunoassay and analyzed using the receiver operating characteristics (ROC) method. RESULTS: The sensitivity and specificity of AFP and DCP for differentiating between early HCC and HBV-associated LC were 51.5% and 92.5%, and 60.0% and 84.7%, respectively. Comparative analysis of ROC curves showed no significant difference in the area under the curve (AUC) for AFP and DCP. Moreover, the combination of AFP and DCP showed the largest AUC value with a diagnostic sensitivity and specificity of 67% and 83.1%, respectively. CONCLUSION: These results suggest that AFP is the best single biomarker for distinguishing between HBV-associated LC and early HCC induced by HBV. However, the combination of AFP and DCP can enhance the diagnostic value of AFP for differentiating between these diseases.

NKG2C+ natural killer cell function improves the control of HBV replication in individuals with acute HIV infection coinfected with HBV.

Individuals infected with hepatitis B virus (HBV) are often coinfected with human immunodeficiency virus (HIV). However, individuals with chronic HBV infection living with acute HIV infection have a significantly lower HBV viral load, along with higher HBeAg and HBsAg loss than HBV-infected individuals alone. Here, we investigated the possible role of natural killer cells (NK cell) function in this progressive course to explore the relationship between phenotypic/functional changes in NK cells during acute HIV infection and HBV clearance in patients with HIV/HBV coinfection.Peripheral blood NK cells from 38 patients with primary HIV infection, including 20 with untreated HIV infection and 18 treatment-naïve patients with HIV/HBV coinfection and 16 patients with chronic HBV infection, were enrolled in this study.We found that the HIV/HBV-coinfected individuals had higher levels of NK cells than the HBV-infected individuals, due to expansion of the CD56 NK cell population. The proportion of NK cells in CD56 and CD56 NK subsets was not found significant difference between HIV/HBV-coinfected and HBV-infected individuals. However, NKG2C levels on NK cells and subsets were significantly higher in HIV/HBV-coinfected individuals than in HBV-infected individuals, whereas NKG2A levels were unaffected or decreased. In addition, the levels of degranulation CD107a, cytotoxicity and IFN-γ production of NK cells were increased in HIV/HBV-coinfected individuals than in HBV-infected individuals. The level of IL-10 production of NK cells was decreased in HIV/HBV-coinfected individuals than in HBV-infected individuals. Furthermore, the level of HBV-DNA was inversely correlated with the proportion of NKG2C and NKG2CNKG2A NK cells, while positively correlated with the proportion of NKG2A and NKG2CNKG2A NK cells. IFN-γ production was inversely correlated with levels of HBV-DNA, but the CD107a expression and IL-10 production of NK cells were not correlated with HBV-DNA levels.These results demonstrate that the upregulation of NKG2C expression, but not of NKG2A expression on the surface of NK cells increases cytolytic capacity and the amounts of cytokines produced and may play a crucial role in HBV clearance during HIV/HBV-coinfection.

A proton-activated, outwardly rectifying chloride channel in human umbilical vein endothelial cells.

Extracellular acidic pH-activated chloride channel I(Cl, acid), has been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to characterize I(Cl,acid) in human umbilical vein endothelial cells(HUVECs). The activation and deactivation of the current rapidly and repeatedly follows the change of the extracellular solution at pH 4.3, with the threshold pH 5.3. In addition, at very positive potentials, the current displays a time-dependent facilitation. pH-response relationship for I(Cl,acid) revealed that EC(50) is pH 4.764 with a threshold pH value of pH 5.3 and nH of 14.545. The current can be blocked by the Cl(-) channel inhibitor DIDS (100 microM). In summary, for the first time we report the presence of proton-activated, outwardly rectifying chloride channel in HUVECs. Because an acidic environment can develop in local myocardium under pathological conditions such as myocardial ischemia, I(Cl,acid) would play a role in regulation of EC function under these pathological conditions.

[Detection of alpha-fetoprotein-L3 using agglutinin-coupled spin column to be used in diagnosis of hepatocellular carcinoma].

OBJECTIVE: To explore the effect of use of lens culinaris agglutinin (LCA)-coupled spin column (ACSC) in detection of alpha-fetoprotein (AFP) isoform AFP-L3 and to evaluate the value of AFP-L3 as a biomarker in diagnosis of hepatocellular-carcinoma (HCC). METHODS: The serum samples of 132 patients with elevated AFP level (20-1000 microg/L), 79 diagnosed as with HCC and 53 with benign liver diseases (35 with liver cirrhosis and 18 with chronic hepatitis) underwent ACSC to isolate the fraction of AFP-L3. The contents of AFP and AFP-L3 were detected by micro-particle immunoassay. The ratio of AFP-L3 to total AFP, AFP-L3%, was calculated. Correlation between the abnormally elevated AFP-L3% and HCC was analyzed. RESULTS: Detection of AFP-L3% using ACSC method was operating friendly. The average value of AFP-L3% in the patients with HCC was 36.4%, significantly higher than those of the patients with benign liver diseases (5.3% respectively, P < 0.01). The area under the receiver operating characteristic (ROC) curve of AFP-L3% was 0.807. Taking AFP-L3% > or = 10% as diagnostic criteria, the sensitivity of AFP-L3% in HCC diagnosis was 84.8% (67/79) and the specificity was 92.5% (49/53), with a total conformity rate of 87.9% compared to the confirmed clinical diagnosis. Conclusion ACSC is of clinical value in detecting AFP-L3. AFP-L3% is a valuable biomarker in diagnosis and prediction of prognosis of HCC.

[A clinical analysis of HBV reactivation in patients with malignant tumors].

OBJECTIVE: To observe the anti-viral therapy effect on HBV reactivation in malignant tumor patients and hepatitis B virus carriers after their cancer chemotherapy. METHODS: Thirteen cancer patients but also chronic hepatitis B virus carriers were enrolled in this study. They were randomly put into two groups. Eight patients were put in the therapeutic group. They all had abnormal liver functions induced by the reactivation of HBV after their cancer chemotherapy. Then they were treated with lamivudine. The other 5 cases were treated with lamivudine before their cancer chemotherapy when their serum HBV DNA levels were less than 10(3) copies/ml (preventive therapeutic group). The two groups were followed-up with liver function tests and serum HBV DNA level measurements. RESULTS: Among the 8 cases of the therapeutic group, 5 cases died of liver failure; cancer chemotherapy was postponed or even terminated in 3 patients due to liver function abnormality and anti-virus treatment was started. In the preventive therapy group, no HBV reactivation was observed in any of the 5 cases. CONCLUSION: For HBV carrier cancer patients, an anti-viral therapy before their cancer chemotherapy seems to be very important.

Targeted Exome Sequencing of Congenital Cataracts Related Genes: Broadening the Mutation Spectrum and Genotype-Phenotype Correlations in 27 Chinese Han Families.

Congenital cataract is the most frequent inherited ocular disorder and the most leading cause of lifelong visual loss. The screening of pathogenic mutations can be very challenging in some cases, for congenital cataracts are clinically and genetically heterogeneous diseases. The aim of this study is to investigate the mutation spectrum and frequency of 54 cartaract-associated genes in 27 Chinese families with congenital cataracts. Variants in 54 cataract-associated genes were screened by targeted next-generation sequencing (NGS) and then validated by Sanger sequencing. We identified pathogenic variants in 62.96% (17/27) of families, and over 52.94% (9/17) of these variants were novel. Among them, three are splicing site mutations, four are nonsense mutations, seven are missense mutations, two are frame shift mutations and one is intronic mutation. This included identification of: complex ocular phenotypes due to two novel PAX6 mutations; progressive cortical cataract and lamellar cataract with lens subluxation due to two novel CRYGS mutations. Mutations were also found in rarely reported genes including CRYBA4, CRYBA2, BFSP1, VIM, HSF4, and EZR. Our study expands the mutation spectrum and frequency of genes responsible for congenital cataracts. Targeted next-generation sequencing in inherited congenital cataract patients provided significant diagnostic information.

[Caspase1 Inhibitor Ac-YVAD-CMK Prevents and Treats the Acute Graft Versus Host Disease in Mice].

OBJECTIVE: To explore the effect of Caspase 1 inhibitor Ac-YVAD-CMK on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) and its mechanism. METHODS: Experiments were divided randomly into 3 groups: allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion group (TS group, n=12), allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion plus injection of low dose Caspase 1 inhibitor group (TS+low dose of C group, n=16) and plus high dose Caspase1 inhibitor (TS+high dose of C group, n=19). The body weight of mice in each group was dynamically detected, and the clinical manifestation of GVHD and score of aGVHD were determined, and the chimerism rate of mice was detected after transplantation for 14 days. Th1, Th2 and Th17 cells in peripheral blood were examined by flow cytometry. Peripheral proinflammatory cytokines IL-1ß, IFN-γ, IL-1α and IL-18 were examined by enzyme-linked immunosorbent assay(ELISA). The tissues sections of GVHD target organs (liver, lung, colon and skin) were stained with HE for histopathologic examination and histopathologic score. RESULTS: Ac-YVAD-CMK could alleviate murine aGVHD and pathological injury, decreare the incidence and severity of aGVHD in recipient mice. The detection of Th cell subsets in peripheral blood by flow cytometry showed that compared with TS group, the Th1 cell ratio in TS+low dose of C and TS+high dose of C groups was significantly reduced (P<0.05), while the Th2 and Th17 cell ratio was significantly enhanced (P<0.05) in TS+low dose of high dose of C groups. The detection of peripheral inflamematory cytokines by ELISA demonstrated that the inflammatory cytokines including IL-1ß,IFN-γ,IL-18 and IL-1α were reduced significantly (P<0.05). CONCLUSION: Ac-YVAD-CMK can improve aGVHD by inhibiting Caspase 1 and reducing the release of some inflammatory cytokines, thereby alleviated the aGVHD pathological damage.

The role of the neutrophil Fcγ receptor I (CD64) index in diagnosing spontaneous bacterial peritonitis in cirrhotic patients.

OBJECTIVE: To investigate the role of the neutrophil Fcγ receptor I (CD64) index in the diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS: A total of 123 cirrhotic patients with ascites who fulfilled the inclusion criteria were enrolled in this study. Ascites and blood samples were collected; the polymorphonuclear neutrophil (PMN) count, bacterial culture, and related laboratory tests were performed. The CD64 index was determined for each sample using flow cytometry. RESULTS: The neutrophil CD64 index results were significantly higher in cirrhotic patients with SBP than in those without SBP (p<0.001). There was a positive correlation between the neutrophil CD64 index and the PMN count in ascites. In the receiver operating characteristic curve (ROC) analysis, the area under the curve (AUC) was 0.894 (95% confidence interval 0.823-0.964, p<0.001). The optimal cut-off value for the neutrophil CD64 index was 2.02. The sensitivity and specificity of the neutrophil CD64 index for cirrhotic patients with SBP were 80.49% and 93.90%, respectively. The elevated neutrophil CD64 index was down-regulated by antibiotic therapy (p=0.002). CONCLUSIONS: The neutrophil CD64 index could be used as a sensitive and specific indicator for the diagnosis of SBP in cirrhotic patients with ascites and is also modulated by antibiotic therapy.

Clinical presentation of hemophagocytic lymphohistiocytosis in adults is less typical than in children.

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P<0.05). 2. Clinical manifestations and laboratory findings: Over 90% of adults and pediatric patients presented with fever, thrombocytopenia and high serum ferritin levels. However, in adults, the proportions of hepatomegaly, splenomegaly and jaundice were much lower (P<0.01) than in children, and serous cavity effusion was more frequent in adult patients (P<0.05). More children had hemoglobin <90 g/L, total bilirubin >19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P<0.05). 3. The time interval from the onset of symptoms to clinical diagnosis was significantly shorter in pediatric patients than in adults (P<0.05). CONCLUSIONS: Certain clinical features were different between the two groups. The less characteristic clinical presentation of hemophagocytic lymphohistiocytosis in adults may make the disease more difficult to diagnose. Our findings suggest that hemophagocytic lymphohistiocytosis should be considered when an adult patient presents with the above-mentioned symptoms.

[The contrast study of Pre-S1 protein, HBV-DNA and HBeAg in diagnosing viral replication in patients with chronic hepatitis B].

OBJECTIVE: To determine the role of Pre-S1 protein in diagnosing viral replication in patients with chronic hepatitis B. METHODS: 104 consecutive patients with chronic hepatitis B were included in the study, liver biopsy were performed in all patients. Serial serum samples were studied with the quantitative determination of HBV-DNA by a quantitative PCR assay, determination of Pre-S1 protein by ELISA. RESULTS: The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg HBeAg anti-HBc (+) both were 96.5%. The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg anti-HBe anti-HBc (+) were 81.5%, 72.3%, respectively. The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg anti-HBc (+) were 87.5%, 75.0%, respectively. It represented some patients with HBeAg (-) anti-HBe (+/-) still had viral replication. HBV-DNA>10(3) copy/ml as positive criteria for diagnosing viral replication, the positive rate of HBeAg, Pre-S1 were 31.5% (28/89), 80.9% (72/89) in patients with HBV-DNA>10(3) copy/ml, respectively. The concordance rates of HBeAg, Pre-S1 with HBV-DNA were 40.0% (42/104), 82.0% (85/104), respectively. CONCLUSION: It showed that Pre-S1 was more sensitive than HBeAg in diagnosing viral replication in patients with chronic hepatitis B.

[The relationship among the counts of platelet, thrombopoietin and spleen index in patients with liver cirrhosis].

OBJECTIVE: To determine the reason of thrombocytopenia in patients with liver cirrhosis, we studied the relationship among platelet counts, serum thrombopoietin (TPO) level and spleen index. METHODS: Serum TPO, platelet counts and spleen index were measured in 71 cirrhotic patients. TPO was measured with ELISA method, spleen index were measured on ultrasonography by the same doctor. RESULTS: Platelet counts in patients with cirrhosis were lower than that of healthy group [(109.20+/-53.39) vs (169.63+/-26.60) x 10(12)/L, P<0.05]. Serum thrombopoietin level in patients with cirrhosis was similar to that of healthy group [(436.42+/-258.97) vs (412.63+/-132.80) pg/ml, P>0.05]. However, serum thrombopoietin level decreased as liver disease aggravated, [(526.13+/-317.44) pg/ml in Child-Pugh grade A, (445.22+/-214.90) pg/ml in grade B and (311.45+/-182.66) pg/ml in grade C, grade A vs. Grade C, P<0.05]. However, decline in platelet counts was accompanied with incline in spleen index coordinately. 35 of 71 cirrhotic patients had normal platelet counts whereas 36 of them had thrombocytopenia. Thrombopoietin levels were higher in non-thrombocytopenia group than in thrombocytopenia group [(529.43+/-282.64) vs. (351.27+/-228.25)pg/ml, P<0.01]; but spleen index of two groups showed no difference [(29.65+/-12.00) vs. (36.35+/-12.68) cm2, P>0.05]. Correlation was found between thrombopoietin level and platelet counts (r=0.252, P=0.025); no correlation was found between spleen index and platelet counts (r=-0.238, P=0.062). CONCLUSION: The decline serum TPO levels might play an important role for thrombocytopenia in patients with liver cirrhosis.

[Preliminary report on primary drilling procedure at the time of hydroxyapatite orbital implant].

OBJECTIVE: To evaluate the clinical effect of the drilling and inserting a motility peg at the time of hydroxyapatite orbital implant. METHODS: After drilling and insertion of a titanium motility peg, a hydroxyapatite orbital implant was inserted in 31 consecutive patients. Of the 31 patients, 23 had been referred for primary enucleation and 8 for secondary implant surgery. The titanium-threaded sleeve was driven into the hydroxyapatite after which the titanium flat-headed peg was inserted into the sleeve before orbital implantation. The flat-headed peg was replaced with a titanium motility/support peg 3 to 7 months later. RESULTS: Follow-up ranged from 3.0 to 11.0 months (mean, 6.9 months). All patients were successfully fit with prostheses. Prosthetic motility was acceptable in each patient. 12 of 31 titanium flat-headed pegs became spontaneously and partially exposed within 3 to 7 months. There were no cases of secondary infection, implant exposure or extrusion of the motility peg. CONCLUSION: The hydroxyapatite orbital implant primary drilling procedure gives good cosmetic results with good motility of the artificial eye. It does not result in increased complications, and is an effective and efficient surgical option.

Reflections on microRNAs in chronic pulmonary disease: looking into the miR-ror and crystal ball.

Chronic respiratory diseases are a significant health problem requiring novel approaches to both complement existing therapies and provide breakthrough medicines. Recent clinical advances in understanding the behavior of inhaled oligonucleotides provide the impetus for application of this technology to microRNA therapeutics. MicroRNAs are evolutionarily conserved small regulatory RNA molecules involved in tuning gene networks controlling biological and pathological processes. Deletion or overexpression of microRNAs results in phenotypic changes in animal models of disease such as cancer, fibrosis, diabetes, and inflammation. Inhibition of microRNAs in preclinical models of asthma, cystic fibrosis, and idiopathic pulmonary fibrosis has shown therapeutic promise. In animals, inhibitors of microRNAs directly delivered to the airway at doses suitable for nebulizers or hand-held inhalers up-regulate expression of cohorts of genes containing complementary "seed" sequences for specific and directed microRNA binding within their mRNA untranslated regions. These observations suggest the opportunity to exploit intervention in microRNA biology to create new therapies for chronic pulmonary disorders.

Diagnostic performance of interferon-gamma releasing assay in HIV-infected patients in China.

BACKGROUND: Active tuberculosis infection represents a very common and significant threat to HIV-infected patients. But measures to accurately detect it are limited. OBJECTIVE: To compare and analyze the diagnostic efficacy of T-SPOT.TB alone and in combination with TST in HIV-infected patients in China. METHOD: TST (tuberculin skin test) and T-SPOT.TB were performed on 131 HIV-infected patients admitted in Beijing You'an Hospital and Beijing Ditan Hospital between Oct, 2010 and Jul, 2012, who were initially diagnosed as suspected ATB (active TB). The patients were further categorized into ATB and Not ATB based on clinical and cultural evidences. The performance of TST and T-SPOT.TB were analyzed and compared. RESULTS: The sensitivity and specificity of T-SPOT.TB were 41.3% and 94.6%, respectively, both higher than TST (12.9% and 91.8%). By combining T-SPOT.TB and TST, the sensitivity did not increase, but specificity was elevated to 100%. TST, T-SPOT.TB and their combinations all performed better in patients with extra-pulmonary diseases than with pulmonary disorders. False-positive T-SPOT.TB results were found to be associated with history of prior TB. In addition, concomitant bacterial infections and low CD4 counts were associated with increased ATB risk. CONCLUSIONS: T-SPOT.TB is superior in screening ATB in HIV-infected patients in China over traditional TST. Additional TST would help to confirm a positive T-SPOT.TB result. Both tests work better for patients with extra-pulmonary conditions.