Simulation of Uterus Active Contraction and Fetus Delivery in ls-dyna.

Vaginal childbirth is the final phase of pregnancy when one or more fetuses pass through the birth canal from the uterus, and it is a biomechanical process. The uterine active contraction, causing the pushing force on the fetus, plays a vital role in regulating the fetus delivery process. In this project, the active contraction behaviors of muscle tissue were first modeled and investigated. After that, a finite element method (FEM) model to simulate the uterine cyclic active contraction and delivery of a fetus was developed in ls-dyna. The active contraction was driven through contractile fibers modeled as one-dimensional truss elements, with the Hill material model governing their response. Fibers were assembled in the longitudinal, circumferential, and normal (transverse) directions to correspond to tissue microstructure, and they were divided into seven regions to represent the strong anisotropy of the fiber distribution and activity within the uterus. The passive portion of the uterine tissue was modeled with a Neo Hookean hyperelastic material model. Three active contraction cycles were modeled. The cyclic uterine active contraction behaviors were analyzed. Finally, the fetus delivery through the uterus was simulated. The model of the uterine active contraction presented in this paper modeled the contractile fibers in three-dimensions, considered the anisotropy of the fiber distribution, provided the uterine cyclic active contraction and propagation of the contraction waves, performed a large deformation, and caused the pushing effect on the fetus. This model will be combined with a model of pelvic structures so that a complete system simulating the second stage of the delivery process of a fetus can be established.

Bufalin suppresses hepatocellular carcinogenesis by targeting M2 macrophage-governed Wnt1/ß-catenin signaling.

BACKGROUND: The interplay of tumor-associated macrophages (TAMs) and tumor cells plays a key role in the development of hepatocellular carcinoma (HCC) and provides an important target for HCC therapy. The communication between them is still on the investigation. Bufalin, the active component derived from the traditional Chinese medicine (TCM) Chansu, has been evidenced to possess anti-HCC activity by directly suppressing tumor cells, while its immunomodulatory effect on the tumor microenvironment (TME) is unclear. PURPOSE: To explore the mechanism of M2 TAM-governed tumor cell proliferation and the inhibitory effect of bufalin on HCC growth by targeting M2 macrophages. METHODS: Morphology and marker proteins were detected to evaluate macrophage polarization via microscopy and flow cytometry. Cellular proliferation and malignant transformation of HCC cells cultured with macrophage conditioned medium (CM) or bufalin-primed M2-CM, were assessed by cell viability, colony formation and soft agar assays. Regulations of gene transcription and protein expression and release were determined by RT-qPCR, immunoblotting, immunoprecipitation, ELISA and immunofluorescence. Tumorigenicity upon bufalin treatment was verified in orthotopic and diethylnitrosamine-induced HCC mouse model. RESULTS: In this study, we first verified that M2 macrophages secreted Wnt1, which acted as a mediator to trigger ß-catenin activation in HCC cells, leading to cellular proliferation. Bufalin suppressed HCC cell proliferation and malignant transformation by inhibiting Wnt1 release in M2 macrophages, and dose-dependently inhibited HCC progression in mice. Mechanistically, bufalin specially targeted to block Wnt1 transcription, thus inactivating ß-catenin signaling cascade in HCC cells and leading to tumor regression in HCC mouse model. CONCLUSION: These results clearly reveal a novel potential of bufalin to suppress HCC through immunomodulation, and shed light on a new M2 macrophage-based modality of HCC immunotherapy, which additively enhances direct tumor-inhibitory efficacy of bufalin.

Simulation of the Childbirth Process in LS-DYNA.

Childbirth or labor, as the final phase of a pregnancy, is a biomechanical process that delivers the fetus from the uterus. It mainly involves two important biological structures in the mother, the uterus-generating the pushing force on the fetus-and the pelvis (bony pelvis and pelvic floor muscles)-resisting the movement of the fetus. The existing computational models developed in this field that simulate the childbirth process have focused on either the uterine expulsion force or the resistive structures of the pelvis, not both. An FEM model including both structures as a system was developed in this paper to simulate the fetus delivery process in LS-DYNA. Uterine active contraction was driven by contractile fiber elements using the Hill material model. The passive portion of the uterus and pelvic floor muscles were modeled with Neo Hookean and Mooney-Rivlin materials, respectively. The bony pelvis was modeled as a rigid body. The fetus was divided into three components: the head, neck, and body. Three uterine active contraction cycles were modeled. The model system was validated based on multiple outputs from the model, including the stress distribution within the uterus, the maximum Von Mises and principal stress on the pelvic floor muscles, the duration of the second stage of the labor, and the movement of the fetus. The developed model system can be applied to investigate the effects of pathomechanics related to labor, such as pelvic floor disorders and brachial plexus injury.

Application of 3D computed tomography in emphysematous parenchyma patients scheduled for bronchoscopic lung volume reduction.

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three-dimensional computed tomography (3D-CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one-way valve were collected and analysed from 2017 to 2020. Three-dimensional-CT image analysis software system was used to analyse the distribution of low-density areas <950 Hounsfield units in both lungs pre- and post- BLVR. Meanwhile, all patients performed standard PFT pre- and post-operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%-47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D-CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer.

Efficacy and safety of Huashi Baidu granule plus Nirmatrelvir-Ritonavir combination therapy in patients with high-risk factors infected with Omicron (B.1.1.529): A multi-arm single-center, open-label, randomized controlled trial.

BACKGROUND: Huashi Baidu granule (HSBD) and Paxlovid (Nirmatrelvir-Ritonavir) are antiviral Chinese patent medicine and western medicine specially developed for treating coronavirus disease 2019 (COVID-19). Their efficacy and safety in treating COVID-19 are still under investigated. PURPOSE: To assess and compare the efficacy and safety of HSBD, Paxlovid, and the combination in treating high-risk patients infected with SARS-CoV-2 Omicron. STUDY DESIGN: The study was a prospective single-center, open-label, randomized, controlled clinical trial conducted from April 18 to June 5, 2022. (ClinicalTrial.gov registration number: ChiCTR2200059390) METHODS: 312 severe patients aged 18 years and older infected with SARS-CoV-2 Omicron from Shuguang Hospital in Shanghai were randomly allocated to HSBD monotherapy (orally 137 g twice daily for 7 days, n = 105), Paxlovid monotherapy (orally 300 mg of Nirmatrelvir plus 100 mg of Ritonavir every 12 h for 5 days, n = 103), or combination therapy (n = 104). The primary outcome was SARS-CoV-2 nucleic acid negative conversion within 7-day treatment. The secondary outcome included hospital discharging conditions, severe conversion of symptom, and adverse events. RESULTS: Of 312 participants, 85 (82%) of 104 in combination therapy, 71 (68%) of 105 in HSBD monotherapy, and 73 (71%) of 103 in Paxlovid monotherapy had a primary outcome event. The hazard ratios of primary outcome were 1.37 (95% CI 1.03 - 1.84, p = 0.012) for combination versus HSBD, 1.28 (0.98-1.69, p = 0.043) for combination versus Paxlovid, and 0.88 (0.66-1.18, p = 0.33) for HSBD versus Paxlovid. There was no statistical difference of efficacy between HSBD and Paxlovid, while combination therapy exhibited more effective than either alone. For secondary outcomes, the hospital discharging rates within 7 days exhibited the significant increase in combination therapy than in HSBD or Paxlovid monotherapy (71% (74/104) vs 55% (58/105) vs 52% (54/103), p < 0.05). The risk of severe conversion of symptom showed no statistical significance among three interventions (1% (1/104) vs 3% (3/105) vs 3% (3/103), p > 0.05). No severe adverse events occurred among combination therapy and monotherapies in the trial. CONCLUSION: For patients with severe COVID-19, HSBD exhibits similar efficacy to Paxlovid, while combination therapy is more likely to increase the curative efficacy of Omicron variant than monotherapies, with few serious adverse events.

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Mendelian Randomization Study of Causal Relationship between Omega-3 Fatty Acids and Risk of Lung Cancer.

Objective: Evidence suggests that omega-3 fatty acid intake exerts a protective effect on lung cancer, but its causal association with risk of lung cancer remains uncertain. This study attempts to clarify the causal effect of omega-3 fatty acids on lung cancer utilizing genome-wide association study (GWAS) data with Mendelian randomization (MR) approach. Methods: This study acquired omega-3 fatty acid data from the UK Biobank and data of lung cancer patients from the Consortium and International Lung Cancer Consortium (ILCCO). Single-nucleotide polymorphisms (SNPs) associated with omega-3 fatty acids were screened as instrumental variables (IVs) in line with the criteria of p < 5E - 8, linkage disequilibrium R 2 > 0.001 and distance < 10000 kb. Through inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, causal association between omega-3 fatty acids and risk of lung cancer was evaluated. Cochran's Q test was applied for a heterogeneity test. The pleiotropy and horizontal pleiotropy among IVs were evaluated via MR-Egger regression intercept analysis. Results: Totally, 42 SNPs associated with omega-3 fatty acids were identified as IVs. According to the results of IVW (OR (95% CI): 0.899 (0.817, 0.990), p = 0.03), MR-Egger (OR (95% CI): 0.856 (0.750, 0.977), p = 0.026), weighted median (OR (95% CI): 0.899 (0.817, 0.990), p = 0.001), simple mode (OR (95% CI): 0.901 (-0.678, 1.199), p = 0.478), and weighted mode (OR (95% CI): 0.859 (0.782, 0.944), p = 0.003), omega-3 fatty acids showed a causal association with low risk of lung cancer. No genetic pleiotropy or horizontal pleiotropy was found according to MR-Egger regression intercept analysis. Conclusion: Our findings provide sufficient evidence that omega-3 fatty acids are causal protective factors of lung cancer. Despite this, further work is required for elucidating the potential mechanisms.

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function.

Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 µg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 µg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis.

Albumin-Based LL37 Peptide Nanoparticles as a Sustained Release System against Pseudomonas aeruginosa Lung Infection.

Pseudomonas aeruginosa (PA) has emerged as a pressing challenge to pulmonary infection and lung damage. The LL37 peptide is an efficient antimicrobial agent against PA strains, but its application is limited because of fast clearance in vivo, biosafety concerns, and low bioavailability. Thus, an albumin-based nanodrug delivery system with reduction sensitivity was developed by forming intermolecular disulfide bonds to increase in vivo LL37 performance against PA. Cationic LL37 can be efficiently encapsulated via electrostatic interactions to exert improved antimicrobial effects. The LL37 peptide exhibits greater than 48 h of sustained released from LL37 peptide nanoparticles (LL37 PNP), and prolonged antimicrobial effects were noted as the incubation time increased. Levels of inflammatory cytokines secreted by peritoneal macrophages, including TNF-α and IL-6, were reduced significantly after LL37 PNP treatment following PA stimulation, indicating that LL37 PNP inhibits PA growth and exerts anti-inflammatory effects in vitro. In a murine model of acute PA lung infection, LL37 PNP significantly reduced TNF-α and IL-1ß expression and alleviated lung damage. The accelerated clearance of PA indicates that LL37 PNP could improve PA lung infection and the subsequent inflammation response more efficiently compared with free LL37 peptide. In conclusion, this excellent biocompatible LL37 delivery strategy may serve as an alternative approach for the application of new types of clinical treatment in future.

Comparative Study of Volatile Compounds and Expression of Related Genes in Fruit from Two Apple Cultivars during Different Developmental Stages.

Aromatic volatile compounds are important contributors to fruit quality that vary among different cultivars. Herein, headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry was used to determine changes in volatile compounds and related gene expression patterns in "Ruixue" and "Fuji" apples (Malus domestica Borkh.) during fruit development and maturation. Volatile compounds detected in the fruit of both cultivars exhibited similar trends across different developmental stages. In the early stages of "Ruixue" fruit development (60 days after full bloom), there were fewer volatile compounds, mainly aldehydes (87.0%). During fruit maturation (180 days after full bloom), the types and amounts of volatile compounds increased, mainly including esters (37.6%), and alkenes (23.2%). The total volatile concentration, the types of major volatile compounds, and their relative content in both cultivars varied across different stages. Gene expression analysis indicated that the upregulation of MdLOX, MdAAT2, and MdADH3 was associated with increased aroma compound content, especially esters, during fruit development in both cultivars. Changes in the expression of MdArAT, MdACPD, MdADH3, MdAAT2, and MdLOX may lead to differences in volatile compounds between apple cultivars.

Corticosteroids alleviate lipopolysaccharide-induced inflammation and lung injury via inhibiting NLRP3-inflammasome activation.

The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)-induced inflammation and ALI. We used corticosteroid treatment for LPS-induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS-stimulated macrophages were used to explore the specific anti-inflammatory effects of corticosteroids on NLRP3-inflammasome in vitro. We found corticosteroids attenuated LPS-induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in Lung. In vitro, when NLRP3-inflammasome was knocked out, inflammatory response of caspase-1 activation and IL-1ß secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase-1 and the maturation of IL-1ß, which depended on inhibiting the nuclear factor-κB (NF-κB) signal pathway activation. However, when corticosteroids intervened the LPS-primed macrophages, it also negatively regulated NLRP3-inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS-induced inflammation and ALI by suppressing both NF-κB signal pathway and mtROS-dependent NLRP3 inflammasome activation.

PM2.5 compromises antiviral immunity in influenza infection by inhibiting activation of NLRP3 inflammasome and expression of interferon-ß.

PM2.5, a major component of air pollutants, has caused severe health problems. It has been reported that PM2.5 index is closely associated with severity of influenza A virus (IAV) infection. However, the underlying mechanisms have not been addressed. NLRP3 inflammasome and type I interferon signaling regulate host defense against influenza infection. The present study investigated the potential effects of air pollutants on host defense against influenza infection in vitro and in vivo. In this study, different concentrations of PM2.5 were pre-exposed to macrophages and mice before IAV infection to assess the negative effects of air pollutants in virus infection. We found that exposure to PM2.5 deteriorated influenza virus infection via compromising innate immune responses manifested by a decrease IL-1ß and IFN-ß production in vitro. Meanwhile, mice exposed with PM2.5 were susceptible to PR8 virus infection due to down-regulation of IL-1ß and IFN-ß. Mechanistically, PM 2.5 exposure suppressed the NLRP3 inflammasome activation and the AHR-TIPARP signaling pathway, by which compromised the anti-influenza immunity. Thus, our study revealed that PM2.5 could alter macrophage inflammatory responses by suppressing LPS-induced activation of NLRP3 inflammasome and expression of IFN-ß during influenza infection. These findings provided us new insights in understanding that PM2.5 combining with influenza infection could enhance the severity of pneumonia.

Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-ß/Smads pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. AIM OF THE STUDY: The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-ß/Smads pathway. MATERIALS AND METHODS: We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 µM) and treated with ASG (10 µM) simultaneously for 24 h. RESULTS: The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-ß/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-ß/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. CONCLUSIONS: AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-ß/Smads pathway.

Regulation of Cell Behavior by Hydrostatic Pressure.

Hydrostatic pressure (HP) regulates diverse cell behaviors including differentiation, migration, apoptosis, and proliferation. Abnormal HP is associated with pathologies including glaucoma and hypertensive fibrotic remodeling. In this review, recent advances in quantifying and predicting how cells respond to HP across several tissue systems are presented, including tissues of the brain, eye, vasculature and bladder, as well as articular cartilage. Finally, some promising directions on the study of cell behaviors regulated by HP are proposed.

LL37 Inhibits Aspergillus fumigatus Infection via Directly Binding to the Fungus and Preventing Excessive Inflammation.

The incidence of Aspergillus fumigatus infection and the rate of resistance to antifungal drugs have sharply increased in recent years. LL37 has been reported as a host defense peptide with broad-spectrum antibacterial activities. However, the role of LL37 during A. fumigatus infection remains unclear. Here, we examined the interaction between LL37 and A. fumigatus and found that synthetic LL37 could directly bind to the surface of A. fumigatus, disrupting the integrity of the cell wall in vitro. LL37 inhibited mycelial growth in a concentration-dependent manner, rather than fungicidal effect even at high concentration (e.g., 20 µM). Interestingly, low concentrations of LL37 (e.g., 4 µM) significantly attenuated mycelial adhesion and prevented the invasion and destruction of epithelial cells. Following LL37 treatment, the levels of proinflammatory cytokines released by A. fumigatus-stimulated macrophages decreased significantly, accompanied by downregulation of M1 type markers. In a mouse model of pulmonary A. fumigatus infection, LL37-treated mice showed lower amounts of fungi load, moderate pathological damage, and reduced proinflammatory cytokines. Further, LL37 transgenic mice (LL37+/+) were examined to investigate the effects of endogenous LL37 in an A. fumigatus infection model and showed lower susceptibility to A. fumigatus infection in comparison with wild-type mice. In addition, LL37 also played a protective role in an immunosuppressed mouse model of A. fumigatus infection. Thus, LL37 inhibits A. fumigatus infection via directly binding to mycelia and reducing excessive inflammation. LL37 or its analogs may therefore constitute potential drug components for A. fumigatus infection.

Viral infection in community acquired pneumonia patients with fever: a prospective observational study.

BACKGROUND: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. METHODS: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. RESULTS: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death. CONCLUSIONS: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross-sectional and observational study in China.

OBJECTIVES: Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China. METHODS: Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement. RESULTS: Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05). CONCLUSIONS: Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention.

The mortality risk factor of community acquired pneumonia patients with chronic obstructive pulmonary disease: a retrospective cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in community acquired pneumonia (CAP) patients. We aimed to investigate the characteristics and mortality risk factors of COPD patients hospitalized with CAP. METHODS: A retrospective cohort study was conducted at Shanghai Pulmonary Hospital and Shanghai Dahua Hospital. Clinical and demographic data in patients diagnosed with CAP were collected between January 2015 and June 2016. Logistic regression analysis was performed to screen mortality risk factors of COPD patients hospitalized with CAP. RESULTS: Of the total 520 CAP patients, 230 (44.2%) patients had been diagnosed comorbid with COPD (COPD-CAP). CAP patients comorbid with COPD patients had higher rate of need for ICU admission (18.3% vs 13.1%) and need for NIMV (26.1% vs 1.4%) than without COPD (nCOPD-CAP). The PSI, CURB-65 and APACHE-II scores in COPD-CAP patients were higher than that in nCOPD-CAP patients (95 vs 79, P < 0.001; 1 vs 1, P < 0.001; 13 vs 8, P < 0.001, respectively). Logistic regression analysis indicated that aspiration, D-dimer > 2.0 µg/mL and CURB-65 ≥ 3 were risk factors associated with in-hospital mortality ((odd ratio) OR = 5.678, OR = 4.268, OR = 20.764, respectively) in COPD-CAP patients. The risk factors associated with 60-day mortality in COPD-CAP patients were comorbid with coronary heart disease, aspiration, need for NIMV (non-invasive mechanical ventilation) and CURB-65 ≥ 3 (OR = 5.206, OR = 7.921, OR = 3.974, OR = 18.002, respectively). CONCLUSIONS: COPD patients hospitalized with CAP had higher rate of need for NIMV, need for ICU admission and severity scores than those without COPD. Aspiration, D-dimer > 2.0 µg/mL, comorbid with coronary heart disease, need for NIMV and CURB-65 ≥ 3 were mortality risk factors in CAP patients comorbid with COPD.

Pulmonary Langerhans cell histiocytosis: analysis of 14 patients and literature review.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an orphan disease in respiratory medicine, which most affects adult smokers. The purpose of this article was to discuss the clinical features, especially the radiologic features of PLCH patients during their hospitalization through a retrospective analysis on clinical data. Furthermore, the current literature was also reviewed. METHODS: Between December 2008 and June 2012, 14 patients with PLCH were assessed at Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Among these patients, seven patients were diagnosed through tissue biopsy from the lung and one patient from enlarged cervical lymph nodes; the rest of six patients were diagnosed based on the clinical-radiological data. The data consisting of demographics, clinical presentation, smoking habits, pulmonary function tests (PFTs) and radiographic image from the medical records was analyzed retrospectively. RESULTS: The average age of patients (11 males and 3 females) was 42.79 (±13.71) years old. All male patients and one female patient had a long smoking history. The common manifestations were cough and exertional dyspnea. Spontaneous pneumothorax was found in three patients. Varieties of pulmonary shadows such as nodular, cystic, patch-like and cord-like were revealed by chest computed tomography (CT) examination. Large Langerhans cells (LCs) were discovered in biopsy tissue by immunohistochemical stains. CONCLUSIONS: PLCH is still an orphan disease and maybe related to smoking. Clinical symptoms such as cough and exertional dyspnea are non-specific. We shall pay attention to recurrent pneumothorax as clinically it is associated with PLCH. The characteristic radiological manifestation is cystic or nodular shadow in the lungs, which plays crucial roles in diagnosing PLCH.

[Construction of plant expression vectors with PMI gene as selection marker and their utilization in transformation of Salvia miltiorrhiza f. alba].

OBJECTIVE: To construct plant expression pCAMBIA1301-PMI by substituting PMI for hygromycin resistance gene in pCAMBIA1301 and obtain transgenic Salvia miltiorrhiza f. alba using PMI-mannose selection system. METHOD: The 6-phosphomannose isomerase gene (PMI) of Escherichia coli was amplified by PCR. Sequence analysis showed that it shared 100% amino acids identities with the sequences of PMI genes isolates reported in the NCBI. Based on pCAMBIA1305, the plant expression pCAMBIA1305-PMI was constructed successfully by substituting PMI for hygromycin resistance gene in pCAMBIA1305. pCAMBIA1305-PMI was transformed into Agrobacterium tumefaciens LBA4404, and then the leaves of S. miltiorrhiza f. alba were inoculated in LBA4404 with pCAMBIA1305-PMI. RESULT: Plant expression pCAMBIA1301-PMI was successfully constructed and the leaves of S. miltiorrhiza f. alba inoculated in LBA4404 with pCAMBIA1305-PMI were selected on medium supplemented with a combination of 20 g x L(-1) mannose and 10 g x L(-1) sucrose as a carbon source. The transformation efficiency rate was 23.7%. CONCLUSION: Genetic transformation was confirmed by PCR, indicating that a new method for obtaining transgenic S. miltiorrhiza f. alba plants was developed using PMI-mannose selection system.