Ethnopharmacological relevance: Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components of Dioscorea quinqueloba which has been used in herbal medicines for treating some inflammatory diseases. Therefore, it may be a potential drug candidate for PF management.Aim of the study: This study aims to elucidate and verify the anti-pulmonary fibrosis effect of gracillin.Methods: We established an in vivo model of PF by treatment of mice with bleomycin (BLM) and an in vitro model by treatment of NIH-3T3 cells with TGF-& beta;1. Pathological changes to the structure of lung tissue, pulmonary function, inflammatory exudation of bronchoalveolar lavage fluid (BALF) and deposition of collagen were detected in vivo, and extracellular matrix (ECM) deposition and migration were evaluated in vitro. The significance of gracillin on STAT3 phosphorylation and nuclear translocation were evaluated by western blotting, immunohistochemistry and immunofluorescence assays. The STAT3 transcriptional activity was quantified with a dual-luciferase reporter assay. Recovery experiments were performed by plasmid-directed overexpression of STAT3.Results: We found that gracillin could improve pulmonary function, reduce lung inflammation and mitigate collagen deposition to ameliorate BLM-induced PF in mice. Gracillin also suppressed TGF-& beta;1-induced increases in ECM deposition biomarkers, including COL1A1, fibronectin, & alpha;-SMA, N-cad and vimentin, and repressed migration in NIH-3T3 cells. Additionally, gracillin suppressed the phosphorylation, nuclear translocation and transcriptional action of STAT3. Furthermore, the decreased ECM deposition and migration upon gracillin treatment were abrogated upon overexpression of STAT3 in NIH-3T3 cells.Conclusions: Gracillin protects against PF by inhibiting the STAT3 axis, providing a safe and efficacious approach to treating PF.

[This corrects the article on p. 1884 in vol. 11, PMID: 30972212.].

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) causing Bloodstream infection (BSI) are associated with high rates of mortality. Nevertheless, only a few studies regarding the epidemiology of CRKP BSI in south China. The purpose of this study was to describe the epidemiology, clinical characteristics, and the mortality of risk factors associated with CRKP causing bloodstream infection. Methods: A retrospective study of patients with CRKP BSI was recruited from teaching hospital in south China from January 2016 to December 2018. Clinical data were collected from medical records. Results: In total, 90 patients with CRKP BSI were enrolled in the study, while 57% (51/90) of the CRKP BSI were obtained from ICU. Most CRKP BSIs originated from hospitals (81; 85%), while the rest (9; 10%) were healthcare-associated. In univariate analysis, gastrointestinal hemorrhage (p=0.029), Pitt bacteremia score (P=0.045), Charlson comorbidity index (p=0.018) and Corticosteroids use (p=0.036) and Septic shock (p=0.001) were associated with the risk factors for mortality. In a multivariate analysis, septic shock (adjusted odds ratio [aOR] 5.591, 95% confidence interval [CI] 1.405-22.246, P=0.015) and Corticosteroids use (aOR 4.148, 95% CI 1.331-12.928, P=0.014) were independently predictors of mortality. Conclusion: Our data showed that the morbidity and mortality of CRKP BSIs patient from ICU and non-ICU was no significant difference. Standardizing operation and improving nurse quality may play an important role in CRKP BSI patient in intensive care unit. Septic shock and Corticosteroids use were the independent factors of CRKP BSI patient mortality. However, the study did not show an association between invasive procedures and the development of CRKP BSI.

Acute lung injury (ALI) is a clinical syndrome characterized by respiratory failure and acute inflammatory response. Myeloid differentiation protein 2 (MD2) has been reported to play a pivotal role in the recognition of LPS and LPS‐mediates inflammatory response. There have been no clinically effective therapeutic drugs for ALI. L6H9, an inhibitor of MD2, showed anti‐inflammatory effects and cardiac protective activity. However, its effect on ALI has not been elucidated. In this study, intratracheal instillation of LPS was employed to induce ALI in rats. L6H9 pretreatment attenuates LPS‐induced pathological variations in lung tissue and pulmonary edema. LPS instillation enhanced lung microvascular permeability, thereby causing inflammatory cells flow into bronchoalveolar lavage fluid (BALF). However, L6H9 inhibited the LPS‐induced upregulation of total protein concentration and the number of inflammatory cells in BALF. In the meantime, macrophages infiltration in lung tissue induced by LPS was also mitigated by L6H9 treatment. Furthermore, L6H9 suppressed LPS‐induced inflammatory cytokines expression in BALF, serum, and lung tissue. It is noteworthy that LPS‐induced MD2/TLR4 complex formation was inhibited by L6H9 in lung tissue. On the whole, these results show that L6H9 can attenuate LPS‐induced ALI in vivo by targeting MD2. Our study provide new candidate for the treatment of ALI.

Purpose. Mycosis fungoides (MF) is the most common T-cell lymphoma, with indolent biologic behavior in the early stage and features of invasive in the tumor stage. The diagnosis of MF is still ambiguous and difficult. We focused on the proteomic profiling change in the pathogenesis of early MF and identified candidate biomarkers for early diagnosis. Methods. We collected peripheral blood samples of MF patients and healthy individuals (HI) performed proteomic profiling analysis using isobaric tags for relative and absolute quantification (iTRAQ) platform. Differently expressed proteins (DEPs) were filtered, and involved biological functions were analyzed through Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software. Results. We identified 78 DEPs including fifty proteins were upregulated and 28 proteins were downregulated in the MF group with HI as a control. Total DEPs were analyzed according to the biological regulation and metabolic process through GO analysis. The pathways of LXR/RXR activation and FXR/RXR activation were significantly activated, in which APOH, CLU, and ITIH4 were involved. The top annotated disease and function network was (Cancer, Organismal Injury and Abnormalities, Reproductive System Disease), with a key node CLU. These DEPs were involved in cancer, including thyroid carcinoma, head and neck carcinoma, and cancer of secretory structure, in which CLU, GNAS, and PKM played an indirect role in the occurrence and development of cancer. Relevant causal network was IL12 (family), which is related to GNAS, PKM, and other DEPs. Conclusion. Proteomic profiling of early-stage MF provided candidate protein biomarkers such as CLU, GNAS, and PKM, which benefit the early diagnosis and understanding of the mechanism of MF development. Besides, lipid metabolism may be one of the pathogenesis of MF, and IL12 was a potential marker for the diagnosis and treatment of early MF.

Introduction: The objective of the present study was to investigate the influence of cigarette smoking on serum and cerebrospinal fluid (CSF) calcium levels in Chinese heavy smokers. Methods: One hundred and sixty-seven male subjects were divided into non-smokers (95) and heavy smokers (72). Serum and CSF calcium concentrations were assayed. Smoking status was recorded and the degree of nicotine dependence (FNTD) was assessed by questionnaire. Analysis of variance was performed to assess the differences among dichotomous groups. Partial correlations between calcium level and FNTD scores were calculated. Results: In this population-based study, heavy smokers had significantly lower serum calcium levels than did non-smokers (p < .01). There was no difference in CSF calcium levels between heavy smokers and non-smokers. The average number of cigarettes smoked per day contributed to the decreased serum calcium levels in heavy smokers, while the age of smoking onset and smoking years did not affect serum levels within the smoker group. Furthermore, serum calcium levels negatively correlated with FNTD items 1, 4, 5, 6 and total scores; however, no correlation between CSF calcium levels and FNTD scores was found. Conclusions: Serum calcium levels decreased significantly in Chinese heavy smokers and were associated with the average number of cigarettes smoked per day and the degree of nicotine dependence in heavy smokers.

OBJECTIVE:Glutamate is an excitatory neurotransmitter in the central nervous system that participates in initiation and maintenance of sleep and wakefulness. The mechanisms involved occur in the brainstem, lateral hypothalamus, and basal forebrain. Our previous study suggested that higher levels of glutamate in cerebrospinal fluid (CSF) contributed to poorer sleep quality. Smoking has been shown to be harmful to sleep quality. In the present study, we recruited non-smokers and heavy smokers and measured the concentration of CSF glutamate in order to investigate the associations among smoking status, sleep quality, and CSF glutamate levels. METHODS:We recruited 147 men (n = 68 non-smokers, 30.31 ± 9.10 years; n = 79 heavy smokers, 34.54 ± 10.71 years). Glutamate concentrations in CSF were measured by spectrophotometry, and subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS:PSQI total scores were significantly higher in heavy smokers than that in non-smokers (p < 0.001). Glutamate concentrations in CSF were lower in heavy smokers than that in non-smokers (p < 0.001). CSF glutamate levels positively correlated with PSQI total scores in the non-smokers group (r = 0.313, p = 0.011, effect size = 0.324). No correlation was found between CSF glutamate levels and PSQI total scores in the heavy smokers group (p > 0.05). Multivariable linear regression analysis showed that years of smoking was contributed to the PSQI total scores (p = 0.008), and cigarettes smoked per day contributed to the decreased CSF glutamate levels in heavy smokers (p = 0.001). CONCLUSION:Poorer subjective sleep quality and lower CSF glutamate concentrations were observed in the heavy smokers group than in the non-smokers group. In addition, lack of correlation was observed between CSF glutamate levels and PSQI scores in the heavy smokers.

Background Endotoxin-induced acute inflammatory diseases such as sepsis, mediated by excessive production of various pro-inflammatory cytokines remain the leading cause of mortality in critically ill patients. Lipopolysaccharide (LPS), the characteristic endotoxin found in the outer membrane of Gram-negative bacteria, can induce the innate immunity system and through Mitogen activated protein kinase (MAPK) and Nuclear Factor-κB (NF-κB), increase the production of inflammatory mediators. Astaxanthin (ASX), a xanthophyll carotenoid, exerts beneficial effects against oxidation, inflammation, and cancer. But poor evidence has been reported that whether it has protective effects on LPS-induced injury. This study aims to investigate the effects of ASX on LPS-induced sepsis and acute lung injury and to demonstrate its mechanisms. Methods Mouse prime macrophage (MPM) challenged with LPS were used for in vitro pharmacological activity and mechanistic studies. Inflammatory facors (tumor necrosis factor-alpha and interleukin-6 levels) in MPM were determined. The mouse models of LPS-induced sepsis and acute lung injury administrated with or without the compound were used for in vivo studies. Results Pre-treatment of MPM with ASX inhibited MAPK/NF-κB signaling pathway, and attenuated LPS-increased inflammatory factors in vitro. In animal models of LPS-induced sepsis and acute lung injury, administration of ASX significantly improved survival and protected lung injury. Subsequently, ASX was shown to suppress LPS-induced inflammatory factors increase, MAPK phosphorylation, and NF-κB activation in vivo. Conclusions ASX exerts impressively protective effects on LPS-induced injury in vitro and in vivo. Taken together, it might be used as a potential candidate for clinical sepsis.

It is very rare that multiple Bowen's disease (BD) and basal cell carcinoma (BCC) lesions develop in a single patient. Routine therapy for the multiple lesions is not satisfactory. The present authors report on a patient who had developed multiple BD and BCC lesions for 12 years after arsenic trioxide treatment for his acute promyelocytic leukemia 20 years before. The patient with multiple lesions was successfully treated with photodynamic therapy.

Primary pulmonary leiomyosarcoma (PPL) is an extremely rare malignant tumor. It has been revealed that PPL may originate from the smooth muscle of the pulmonary parenchyma, pulmonary arteries and bronchi. Patients with PPL may be asymptomatic or present with symptoms similar to those observed in other primary lung tumors. The present study reports the case of a 48-year-old man who presented with a lung mass and underwent a right upper-middle lobe bronchoscope tumor resection. The patient was subsequently diagnosed with PPL. Following the bronchoscopic tumor resection, chemotherapy was administered to the patient; however, the patient succumbed to the disease after the second cycle of chemotherapy.

Aims: The aim of this study was to investigate the clinical characteristics of pulmonary cryptococcosis occurring in non-HIV patients, and to develop early diagnosis of pulmonary cryptococcosis in immunocompetent cases as well. Methods: We retrospectively reviewed the clinical data of 41 non-HIV infected patients with pulmonary cryptococcosis who were admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2006 to April 2014. Results: The study included a total of 41 patients (23 males and 18 females) with mean age of 47 years. 12.19% of patients had a history of direct exposure to pigeon droppings; 31.70% of the patients' working or living environments were potentially contaminated by fungal spores. Almost one-third of the patients involved into the study were asymptomatic. The most common clinical manifestations were cough, expectoration and hemoptysis. The most common radiological manifestation was single node or mass in lung, which was described as untypical. Of all cases, 11 patients were diagnosed by CT-guided percutaneous cutting needle biopsy (PCNB), 5 patients were diagnosed by operation, and Crytococcus spore was found in 7 patients' cerebrospinal fluid. 8 patients' blood Cryptococcus Neoformans capsular polysaccharide antigens latex agglutination tests were positive. 36 patients received antifungal therapy. 5 patients underwent surgical resection. During 6 to 24 months follow-up, 40 cases showed total recovery and 1 cases showed improvement. Conclusions: Pulmonary cryptococcosis in non-HIV subjects might be related to fungus-contaminated environmental exposure. The great variations and protean manifestations of its clinical features often lead to misdiagnosis. Recognition and invasive examination of non-HIV infected patients' pulmonary cryptococcosis in the early stage may help with improvement of its diagnosis and prognosis.

在呼吸内科临床教学中采用基于标准化病人的TBL联合CBL教学法，能够大大提高学生人际交往能力、口头表达能力、学习积极性、自学能力及理论考核成绩和临床实践能力，为社会培养综合素质较高的医学人才。

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial remodeling mainly due to excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Salidroside, an active ingredient isolated from Rhodiola rosea is proposed to exert protective effects against PAH. However, the function of salidroside in PAH has not been investigated systematically and the underlying mechanisms are not clear. To investigate the effects of salidroside on PAH, the mice in chronic hypoxia model of PAH were given by an increasing concentration of salidroside (0, 16 mg/kg, 32 mg/kg, and 64 mg/kg). After salidroside treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary arterial remodeling were attenuated, suggesting a protective role played by salidroside in PAH. To explore the potential mechanisms, the apoptosis of PASMCs after salidroside treatment under hypoxia conditions were determined in vivo and in vitro, and also the mitochondria-dependent apoptosis factors, Bax, Bcl-2, cytochrome C, and caspase 9 were examined. The results revealed that salidroside reversed hypoxia-induced cell apoptosis resistance at least partially via a mitochondria-dependent pathway. In addition, salidroside upregulated the expression of adenosine A2a receptor (A2aR) in lung tissues of mice and in PASMCs in vitro after hypoxia exposure. Combined the evidence above, we conclude that salidroside can attenuate chronic hypoxia-induced PAH by promoting PASMCs apoptosis via an A2aR related mitochondria dependent pathway.

Obstructive sleep apnea syndrome (OSAS) has been recognized as an important risk factor for cardiovascular morbidity and mortality. However, the underlying mechanisms are poorly understood. Present study aimed to investigate the role of NF-κB-dependent inflammation pathways in pathophysiological responses of cardiovascular system in OSAS.

探索以团队为基础(Team-Based Learning,TBL)及病例引导为基础(Case-Based Learning,CBL)的教学模式,并通过标准化病人(Standarized Patients,SP)结合CBL在呼吸系统临床教学中进行应用.参加学生理论成绩和临床实践能力大幅提升,人际交往和口头表达能力、人文关怀能力、主动学习和自我学习能力均明显提高.

OBJECTIVE:To investigate the clinicopathological features of primary intravascular large B-cell lymphoma (IVLBCL) of the lung.METHODS:Histopathological and clinical data based on lung biopsy were analyzed and used to diagnose a patient with IVLBCL of the lung.RESULTS:Fever and respiratory symptoms were the main presentations, lung biopsy revealed lymphoma cells in the lumen of small blood vessels. Tumor cells expressed Bcl-2, the Bcl-6, CD20, Ki67, MUM-1, Pax5, CD, CD30, and vascular endothelial CD34.CONCLUSIONS:Primary pulmonary IVLBCL of the lung is extremely rare, on chest CT it manifests as diffuse ground glass shadow, or nodular consolidations in the lung, lactate dehydrogenase and C-reactive protein was found to increase, fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an important and significant diagnostic modality in its early diagnosis. Also, bronchial lung biopsy has the advantage of less trauma and high sensitive rate. R-CHOP is the main treatment for lung primary pulmonary IVLBCL of the lung; however, its prognosis is relatively poor.

Central sterile supply department(CSSD) is an important unit of hospitals. With the use of RFID technology, it can not only realize intelligent closed-loop management and equipment tracking of operation package, but can also strengthen the quality monitoring of cleaning, disinfection and sterilization process, optimize the supply department process, promote the integration management of operation room and supply department. It can not only improve the efficiency of hospitals, but also can guarantee the safety of patients and accumulate experience for the construction of hospital internet of things.

目的 探究急性肺栓塞后大鼠肺组织中MCP-1的表达及p38 MAPK信号通路对MCP-l的影响.方法 通过自体血栓回输法复制大鼠急性肺栓塞模型,分成1、4、8h组.采用免疫组化法检测急性肺栓塞大鼠MCP-1、p38 MAPK磷酸化蛋白的表达,采用半定量RT-PCR检测急性肺栓塞大鼠肺组织MCP-1 mRNA的表达,采用Western blot检测急性肺栓塞大鼠肺组织p-p38 MAPK表达.结果 免疫组化检测结果显示MCP-1、p-p38 MAPK在大鼠肺组织中有明显表达,RT-PCR、Western blot 检测结果显示急性肺栓塞后大鼠肺组织中MCP-1 mRNA、p-p38 MAPK的表达水平随时间点有明显升高,且两者呈正相关.结论 急性肺栓塞大鼠MCP-1表达水平明显升高,其机制可能是肺栓塞后p38 MAPK通路被激活实现的.

The identification of the relevant thermostable region is one of the key issues in protein thermostability transformation. In this paper, we used SUBTILISIN BPN as our research object, and the conservative and strong coupling residues were extracted by the statistical coupling analysis (SCA) of homologous sequences of SUBTILISIN BPN family. We also extracted SUBTILISIN BPN surface candidate mutant residues by the way of molecular dynamics simulation. Combination of the above results, the recognition method of critical regions of the thermostability transformation on SUBTILISIN BPN surface was proposed. This method determined the SUBTILISIN BPN of 10 critical areas on surface about the thermostability transformation, and compared the results with existing experimental data of thermostable mutations , found that 7 of the forecast areas coincided with the experimental results. The results verified that our method can recognise the protein thermostable transformation critical areas well.

Paeoniflorin (PF), which is the main active ingredient in the root of Paeonia Radix, has many pharmacological effects. Here, we investigated the effect of PF on rat pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions and explored the mechanisms of the effects. The anti-proliferative effect of PF increased in a dose dependent manner. At the highest dose (20 μmol/L), the anti-proliferative effect of PF peaked at 24 h after administration. However, the selective A2B adenosine receptor (A2BAR) antagonist MRS1754 abolished it. PF increased A2BAR mRNA levels from 0.0763±0.0067 of β-actin mRNA levels (hypoxia group) to 0.1190±0.0139 (P<0.05) measured by Real Time Reverse Transcription-Polymerase Chain Reaction. A2BAR protein expression measured by Western Blot was also increased. PF inhibited the proliferation of PASMCs by blocking cell cycle progression in the S phase. These data indicated that activation of A2BAR might be involved in the anti-proliferative effect of PF on PASMCs under hypoxic conditions. The results suggested that a new mechanism of PF could be relevant to the management of clinical hypoxic pulmonary hypertension.