[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

[Expert consensus for diagnosis and treatment of thrombocytopenia in China].

Thrombocytopenia is the main clinical manifestation or common complication of multiple diseases, but there is still a lack of systematic understanding of pathogenesis, underlying diseases and treatment strategies of thrombocytopenia. Based on evidence-based medicine, this consensus summarizes seven aspects related to thrombocytopenia, including definition, epidemiology, pathogenesis, clinical manifestations, laboratory examination, diagnosis and treatment. This consensus provides an important reference for the diagnosis and treatment of thrombocytopenia.

[Precise therapy for lung cancer patients with rare sensitive mutations of epidermal growth factor receptor].

Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45% and 40%, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations. Some previous retrospective studies of small sample size and case reports showed that most of EGFR exon19 (Ins), exon 21 (L861), exon 18 (G719X) and exon20 (S768I) mutations were sensitive to TKIs. And although the exon 20 insertion mutation is usually predicted to the first and second generations of EGFR-TKIs resistance, some specific types are sensitive to the third generation of EGFR-TKIs. Currently, targeted drugs for Ins20 -Ap32788 mutation has entered into clinical trials. Patients with complex mutations have similar efficacy on EGFR-TKIs in comparison with those with single sensitivity mutations. In conclusion, when patients with rare sensitive mutations received EGFR-TKIs therapy, the efficacy and progression-free survival time is similar to or slightly lower than those with classical sensitive mutations, whereas it is higher than those with wild-type EGFR. Compared with the first generation of EGFR-TKIs, second generation EGFR-TKIs may be more suitable for the treatment of lung cancer patients harboring rare sensitive EGFR mutations.

Perfluorocarbon inhibits lipopolysaccharide-induced macrophage inflammatory protein-2 expression and activation of ATF-2 and c-Jun in A549 pulmonary epithelial cells.

The signaling pathway that mediates the anti-inflammatory effects of perfluorocarbon (PFC) in alveolar epithelial cells treated with lipopolysaccharide (LPS) remains unclear. To evaluate the role of macrophage-inflammatory protein-2 (MIP-2), four A549 treatment groups were utilized: (1) untreated control, (2) 10 µg/mL of LPS, (3) 10 µg/mL of LPS+30% PFC and (4) 30% PFC. MIP-2 mRNA expression was determined by qPCR and ELISA. Mitogen-activated protein kinase (MAPK) activation was determined by Western blot analysis, and MIP-2 expression was determined by qPCR following treatment with MAPK inhibitors. PFC suppressed LPS-induced MIP-2 mRNA levels (P≤0.035) and MIP-2 secretion (P≤0.046). LPS induced ATF-2 and c-Jun phosphorylation, which was suppressed by PFC. Finally, inhibitors of ERK, JNK, and p38 suppressed LPS-induced MIP-2 mRNA expression. Thus, PFC inhibits LPS-induced MIP-2 expression and ATF-2 and c-Jun phosphorylation. To fully explore the therapeutic potential of PFC for acute lung injury (ALI), in vivo analyses are required to confirm these effects.

Fecal detection of enterotoxigenic Bacteroides fragilis.

Bacteroides fragilis is a common colonic symbiote of which one subtype, enterotoxigenic Bacteroides fragilis (ETBF), causes inflammatory diarrhea. However, asymptomatic ETBF colonization is common. Through its primary virulence factor, B. fragilis toxin (BFT), ETBF causes asymptomatic, chronic colitis in C57BL/6 mice and increased colon tumorigenesis in multiple intestinal neoplasia mice. Human studies suggest an association between ETBF infection, inflammatory bowel disease, and colon cancer. Additional studies on ETBF epidemiology are, therefore, crucial. The goal of this study is to develop a reliable fecal diagnostic for ETBF. To develop a sensitive assay for ETBF, we tested multiple protocols on mouse stools spiked with serially diluted ETBF. Each assay was based on either touchdown or quantitative polymerase chain reaction (qPCR) and used primers targeted to bft to detect ETBF. Using touchdown PCR or qPCR, the mean ETBF detection limit was 1.55 × 10(6) colony-forming units (CFU)/g stool and 1.33 × 10(4) CFU/g stool, respectively. Augmentation of Bacteroides spp. growth in fecal samples using PYGB (Peptone Yeast Glucose with Bile) broth enhanced ETBF detection to 2.93 × 10(2) CFU/g stool using the touchdown PCR method and 2.63 × 10(2) CFU/g stool using the qPCR method. Fecal testing using combined culture-based amplification and bft touchdown PCR is a sensitive assay for the detection of ETBF colonization and should be useful in studying the role of ETBF colonization in intestinal diseases, such as inflammatory bowel disease and colon cancer. We conclude that touchdown PCR with culture-based amplification may be the optimal ETBF detection strategy, as it performs as well as qPCR with culture-based amplification, but is a less expensive technique.

Bariatric surgery is associated with increased risk of new-onset inflammatory bowel disease: case series and national database study.

BACKGROUND: Case series suggest a possible association between bariatric surgery and incident IBD. AIM: The aim of this study was to evaluate the association between bariatric surgery and new-onset IBD. METHODS: We first conducted a multi-institutional case series of patients with a history of IBD and bariatric surgery. We next conducted a matched case-control study using medical and pharmacy claims from 2008 to 2012 in a US national database from Source Healthcare Analytics LLC. Bariatric surgery was defined by ICD-9 or CPT code. Bariatric surgery was evaluated as recent (code in database timeframe), past (past history V code) or no history. Conditional logistic regression was used to estimate odds ratios (OR) and 95% CI for new-onset IBD, CD and UC. RESULTS: A total of 15 cases of IBD (10 CD, 4 UC, 1 IBD, type unclassified) with a prior history of bariatric surgery were identified. Most cases were women, had Roux-en-Y surgery years prior to diagnosis and few IBD-related complications. A total of 8980 cases and 43 059 controls were included in our database analysis. Adjusting for confounders, a past history of bariatric surgery was associated with an increased risk of new-onset IBD (OR 1.93, 95% CI 1.34-2.79). However, patients who had recent bariatric surgery did not appear to be at shorter term risk of IBD (OR 0.94, 95% CI 0.58-1.52). CONCLUSION: New-onset IBD was significantly associated with a past history of bariatric surgery. This potential association needs to be confirmed in future prospective studies.

Decreased Gs alpha mRNA levels accompany the fall in Gs and adenylyl cyclase activities in compensated left ventricular hypertrophy. In heart failure, only the impairment in adenylyl cyclase activation progresses.

We have previously reported that there is a global reduction in adenylyl cyclase associated with a decrement in Gs functional activity in cardiac sarcolemma from animals with pressure overload-induced hypertrophy and heart failure. This study was performed to determine whether hypertrophy alone in the absence of heart failure is sufficient to promote these changes and whether the superimposition of heart failure intensified these changes. Basal and stimulated adenylyl cyclase and Gs activity, as determined in the S49 cyc- reconstitution assay, were measured in sarcolemma from normal (NL), left ventricular hypertrophy (LVH) and heart failure (HF) animals. Simultaneously, we measured the mRNA level encoding for the Gs alpha subunit. These studies indicate that Gs activity and Gs alpha mRNA are decreased by approximately 30% both in the failing heart and even in the heart with compensated hypertrophy before heart failure develops (Gs activity, pmol cyclic AMP/10 min per microgram, NL 4.2 +/- 0.4, LVH 3.0 +/- 0.2, HF 3.2 +/- 0.3; Gs alpha mRNA, pg/10 micrograms RNA, NL 131 +/- 9.0, LVH 104 +/- 7.4, HF 97.4 +/- 9.1; P less than 0.05 as compared with NL for LVH and HF). Accompanying this decrement in Gs activity is a fall in adenylyl cyclase, both basal and stimulated. However, we also identified a further decrease in adenylyl cyclase without any additional change in Gs or in its alpha subunit mRNA level. This is seen only in the sarcolemma from animals with heart failure as compared with those with compensated LV hypertrophy (e.g., NaF-stimulated activity, pmol cyclic AMP/min per mg, NL 420.2 +/- 17.5, LVH 347.1 +/- 29.6, HF 244.2 +/- 27.3; P less than 0.05 compared with NL for LVH and HF, P less than 0.05 compared with LVH for HF). In summary, these studies indicate that both Gs and adenylyl cyclase activities fall in parallel with the development of LV hypertrophy followed by a further decrement in adenylyl cyclase, independent of Gs, in the setting of heart failure.

Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease.

BACKGROUND: Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. AIM: To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. METHODS: Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. RESULTS: Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients. CONCLUSIONS: FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity.

Mothers' knowledge about children's play and language development: short-term stability and interrelations.

Sixty-four mothers of children ranging in age from 6 to 58 months were asked to determine, for pairings of play and language items, which item was more advanced developmentally. This procedure was repeated within 2 weeks. In general, mothers' orderings of play and language items matched those established in the developmental literature and were stable over the short term. Mothers' knowledge about language development was stronger than and unrelated to their knowledge about play, suggesting that maternal knowledge about developmental domains is differentiated and specific. Finally, mothers' judgments about the developmental milestones depended on their children's current developmental stage: Mothers were less accurate at estimating the timing of milestones that their children had mastered many months earlier, supporting the view that mothers' knowledge is informed by their children's recent rather than past achievements in specific areas.

Parrot breeder's lung: first case report in China.

The authors report the first case of parrot breeder's lung in China and the study of its immunology, respiratory physiology, as well as pathology. The main characteristics of this disease are progressive dyspnea after contacting parrots, patchy or reticular shadows in the lower lung fields on chest X-ray, the presence of alveolitis, accompanied by pulmonary interstitial fibrosis as demonstrated in lung biopsy, restrictive or mixed ventilation disorders with reduction of diffusing capacity and lung compliance. The results of specific ring precipitation test and counter immunoelectrophoresis were helpful in diagnosis. The importance of early diagnosis and treatment is also discussed.

[Complications of mechanical ventilation. A clinical analysis of 82 cases].

The complications of mechanical ventilation were analysed retrogradely in 82 cases with respiratory failure treated in ICU in recent 5 years. There were 48 males and 34 females ranging from 28 to 82 years of age (mean age: 57.1 +/- 16.8). In 82 cases, 6 cases had complications of barotrauma, 39 cases, of infections, 15 cases, of hypotension, 24 cases, of arrhythmia, 14 cases, of upper gastrointestinal hemorrhage and 10 cases, of multiple organ failure. The total incidence of complication was 76.8%. Exactly within three days of mechanical ventilation, the incidence of complication was 31.3%, while beyond three days, it was 87.9%. It was indicated that the mortality increased significantly in the cases with severe complications such as, multiple organ failure. The causes of all kinds of complications and their prevention as well as treatments were discussed.

[Nd-YAG laser treatment of tracheobronchial lesions].

From January 1987 to May 1988, 32 cases with tracheobronchial lesions were treated with Nd-YAG laser. Complete restoration of the airway was achieved in one case of leiomyoma, adenoma, carcinoid and mucous epithelioma each, 2 cases of polyp and 7 cases of granuloma. Significant restoration was seen in one case of granuloma, 2 cases of hematoma and papilloma, each, 3 cases of amyloidosis and partial restoration in one case of granuloma. The remaining 10 cases with squamous cell carcinoma and adenocarcinoma with severe airway obstruction were treated by Nd-YAG laser for palliative purpose only. Four of them revealed significant remission and 6 responded with partial remission. No severe complication was observed during or after the procedures. Nd-YAG laser treatment provides a new curative method avoiding resection of the lung in benign lesions and a palliative therapy for unresectable obstructive malignant tumors.

Rotational relaxation of the "microviscosity" probe diphenylhexatriene in paraffin oil and egg lecithin vesicles.

The rotational relaxation of the widely used "microviscosity" probe, 1,6-diphenyl-1,3,5-hexatriene, was examined by the technique of nanosecond time-resolved fluorescence depolarization. The decays of the emission anisotropy were determined at five temperatures in the range 3-31 degrees both in a reference paraffin oil and in sonicated egg lecithin vesicles. These decays were complex in both media. Marked qualitative as well as quantitative differences were observed in the rotational behavior of the probe in the complex bilayer medium as opposed to the homogeneous reference solvent. The results are discussed in relation to the structure of the hydrophobic bilayer membrane interior and the concept of its "microviscosity".

Nanosecond time-dependent fluorescence depolarization of diphenylhexatriene in dimyristoyllecithin vesicles and the determination of "microviscosity".

The nanosecond time dependence of the fluorescence depolarization of 1,6-diphenyl-1,3,5-hexatriene in L-alpha-dimyristoyllecithin vesicles was determined at temperatures above and below the midpoint of the gel-liquid crystalline transition. In neither case could the decay of the total fluorescent emission or the decay of the emission anisotropy be described adequately in terms of single exponential decay laws. At the lower temperature, the emission anisotropy did not approach zero in the time window available for measurement, a finding which may indicate that the range over which rotation of the probe can freely occur is restricted. The results are discussed in relation to the concept of microviscosity of bilayer membranes.

Effects of endothelin-1 on isolated uterine horns in estrogen-primed and pregnant mice.

Mouse uterine horns from 4 states (estrogen-primed and early-, mid-, and late-pregnancy) were used to study the effect of endothelin-1 (ET) vs carboprost (Car) and oxytocin (Oxy). In K(+)-Krebs (KCl 40 mmol.L-1) solution, ET (1-300 nmol.L-1), Car (0.002-20 mumol.L-1), and Oxy (0.6-60 nmol.L-1) evoked concentration-dependent increases in tension of the uterine horns from 4 different states. Emax for ET were 1.12 +/- 0.26, 1.27 +/- 0.18, and 1.49 +/- 0.13 g in early-, mid-, and late-pregnancies, respectively. Emax for Car in mid- was twice that in late-pregnancy, whereas Emax for Oxy in late- was thrice that in mid-pregnancy. EC50 for ET were 9.6, 5.8, and 6.3 nmol.L-1 in early-, mid-, and late-pregnancies, respectively, and were only 2% to 7% of that for Car and 3-15 times of that for Oxy in various gravid stages. The results suggest that the contractile activity of pregnant mouse uterus to ET is more potent than that of Car while slightly weaker than that of Oxy.