Publications by authors named "Chun Pan"

97 Publications

Single-Nucleotide Polymorphisms Related to Leprosy Risk and Clinical Phenotypes Among Chinese Population.

Pharmgenomics Pers Med 2021 12;14:813-821. Epub 2021 Jul 12.

Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, People's Republic of China.

Background: Genome-wide association studies (GWASs) have identified some immune-related single-nucleotide polymorphisms (SNPs) to be associated with leprosy.

Methods: This study investigated the association of 17 SNPs based on previously published GWAS studies with susceptibility to leprosy, different polar forms and immune states of leprosy in a case-control study from southwestern China, including 1344 leprosy patients and 2732 household contacts (HHCs) (1908 relatives and 824 genetically unrelated contact individuals). The differences of allele distributions were analyzed using chi-squared analysis and logistic regression.

Results: After adjusting covariate factors, rs780668 and rs3764147 polymorphisms influenced susceptibilities to genetically related or unrelated leprosy contact individuals. rs142179458 was associated with onset early cases, rs73058713 A allele and rs3764147 A allele increased the risk of reversal reaction, while rs3764147 G allele had higher risk to present lepromatous leprosy and erythema nodosum leprosum.

Conclusion: Our results demonstrated that genetic variants in the and genes were positively correlated with the occurrence of leprosy and leprosy clinical phenotypes, providing new insights into the immunogenetics of the disease.
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http://dx.doi.org/10.2147/PGPM.S314861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285297PMC
July 2021

Predictive nomogram for leprosy using genetic and epidemiological risk factors in Southwestern China: Case-control and prospective analyses.

EBioMedicine 2021 Jun 26;68:103408. Epub 2021 May 26.

Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China.; National Centre for Leprosy Control, China CDC, Nanjing, China; Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

Background: There is a high incidence of leprosy among house-contacts compared with the general population. We aimed to establish a predictive model using these genetic factors along with epidemiological factors to predict leprosy risk of leprosy household contacts (HHCs).

Methods: Weighted genetic risk score (wGRS) encompassing genome wide association studies (GWAS) variants and five non-genetic factors were examined in a case-control design associated with leprosy risk including 589 cases and 647 controls from leprosy HHCs. We constructed a risk prediction nomogram and evaluated its performance by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling with 1000 resamples and a prospective design including 1100 HHCs of leprosy patients.

Finding: The C-index for the risk model was 0·792 (95% confidence interval [CI] 0·768-0·817), and was confirmed to be 0·780 through bootstrapping validation. The calibration curve for the probability of leprosy showed good agreement between the prediction of the nomogram and actual observation. HHCs were then divided into the low-risk group (nomogram score ≤ 81) and the high-risk group (nomogram score > 81). In prospective analysis, 12 of 1100 participants had leprosy during 63 months' follow-up. We generated the nomogram for leprosy in the validation cohort (C-index 0·773 [95%CI 0·658-0·888], sensitivity75·0%, specificity 66·8%). Interpretation The nomogram achieved an effective prediction of leprosy in HHCs. Using the model, the risk of an individual contact developing leprosy can be determined, which can lead to a rational preventive choice for tracing higher-risk leprosy contacts.

Funding: The ministry of health of China, ministry of science and technology of China, Chinese academy of medical sciences, Jiangsu provincial department of science and technology, Nanjing municipal science and technology bureau.
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http://dx.doi.org/10.1016/j.ebiom.2021.103408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176313PMC
June 2021

A purified acidic polysaccharide from Sarcandra glabra as vaccine adjuvant to enhance anti-tumor effect of cancer vaccine.

Carbohydr Polym 2021 Jul 19;263:117967. Epub 2021 Mar 19.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Immunological adjuvants are an important part of tumor vaccines and are critical for stimulating anti-tumor immune responses. However, the clinical needs of strong adjuvants have not been met. In this work, we found that the purified acidic polysaccharide from Sarcandra glabra, named p-SGP, is an ideal adjuvant for tumor vaccines. Cancer vaccines could induce stronger humoral and cellular immune responses when they are adjuvanted with p-SGP. Compared with CpG, a well-studied adjuvant, p-SGP significantly augmented the anti-tumor immunity of various cancer vaccines, which is leading to noticeable inhibition of tumor growth and metastasis in tumor-bearing mice. Moreover, p-SGP promoted dendritic cells (DCs) maturation and Th1-polarized immune response. Toll-like receptor 4 (TLR4) inhibitor TAK-242 could significantly inhibit the expression of mature molecules on the surface of DCs stimulated by p-SGP, suggesting that p-SGP could play the role of activating DCs through the TLR4 receptor. Results of RNA-seq showed that the Delta-like ligand 4 (DLL4) gene in the pathway Th1 and Th2 cell differentiation was significantly up-regulated in the DCs treated with p-SGP, suggesting that p-SGP has a unique mechanism of enhancing anti-tumor immunity.
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http://dx.doi.org/10.1016/j.carbpol.2021.117967DOI Listing
July 2021

Intra-abdominal infection in acute pancreatitis in eastern China: microbiological features and a prediction model.

Ann Transl Med 2021 Mar;9(6):477

Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: This study aimed to investigate the microbiol distribution of intra-abdominal infection in patients with acute pancreatitis, and to develop a reliable prediction model to guide the use of antibiotics.

Methods: Inpatient with acute pancreatitis between January 2015 and June 2020 were enrolled in the study. Participants were divided into the intra-abdominal infection group and non-infection group. Isolated pathogens and antibiotic susceptibility were documented. Characteristics parameters, laboratory results, and outcomes were also compared. Least absolute shrinkage and selection operator (LASSO) regression model was used to select the risk factors associated with intra-abdominal infection in patients with acute pancreatitis. Logistic regression analysis, random forest model, and artificial neural network were also used to validate the performance of the selected predictors in intra-abdominal infection prediction. A novel nomogram based on selected predictors was established to provide individualized risk of developing intra-abdominal infection in patients with acute pancreatitis.

Results: A total amount of 711 participants were enrolled in the study, and of these, 182 (25.6%) had intra-abdominal infection. Of the 247 isolated pathogens, 45 (18.2%) were multidrug-resistant bacteria, and antibiotic susceptibility was lower than that of China Antimicrobial Surveillance Network 2020. The LASSO method identified 5 independent predictors [intra-abdominal pressure (IAP), acute physiology and chronic health evaluation II (APACHE II), computed tomography severity index (CTSI), the severity of pancreatitis, and intensive care unit (ICU) admission] of intra-abdominal infection, which were validated by three different models. The area under the curve was >0.95 for all 5 predictors. A clinically useful nomogram based on these predictors was successfully established.

Conclusions: Multidrug-resistant bacteria were quite common in intra-abdominal infection. IAP, APACHE II, CTSI, the severity of pancreatitis, and ICU admission were identified as risk factors and the new nomogram based on these could help clinicians estimate the risk of intra-abdominal infection and optimize antimicrobial prescription for acute pancreatitis patients.
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http://dx.doi.org/10.21037/atm-21-399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039642PMC
March 2021

SOX9 in prostate cancer is upregulated by cancer-associated fibroblasts to promote tumor progression through HGF/c-Met-FRA1 signaling.

FEBS J 2021 Mar 11. Epub 2021 Mar 11.

Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, China.

Transcription factor SOX9 was a biomarker for prostate cancer (Pca) with poor prognosis. Nevertheless, the regulatory mechanism underlying SOX9 upregulation still remains unclear. Several cytokines have been reported to be involved in the regulation of SOX9, suggesting that cancer-associated fibroblasts (CAFs), one of the main sources of secreted factors in the tumor microenvironment (TME), may play a role in regulating SOX9 expression. Herein, an in vitro model of paracrine interaction between primary CAFs and Pca cells was applied to investigate the molecular mechanism of SOX9 upregulation during Pca progression. The regulatory axis was validated by in vivo experiments and The Cancer Genome Atlas data. Conditional medium of CAFs (CAF-CM) upregulated the expression of SOX9, which was mutually proved to be essential for CAF-induced tumor progression. Further analysis showed that hepatocyte growth factor (HGF) secreted by CAFs was responsible for SOX9 elevation in Pca cells, via the activation of c-Met signaling. Mechanistically, HGF/c-Met signaling specifically activated MEK1/2-ERK1/2 pathway, which induced phosphorylation and upregulation of FRA1, which then transcriptionally upregulated SOX9 by binding to the promoter of SOX9 gene. Moreover, we identified that HGF/c-Met-ERK1/2-FRA1-SOX9 axis was relatively conserved between human and mouse species by validating in mouse Pca cells. Our results reveal a novel insight into the molecular mechanism that SOX9 in Pca cells is promoted by CAFs through HGF/c-Met-ERK1/2-FRA1 axis. Furthermore, SOX9 may serve as an alternative marker for the activated HGF/c-Met signaling to enroll the optimal Pca patients for HGF/c-Met inhibition treatment, since it is much more stable and easier to detect.
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http://dx.doi.org/10.1111/febs.15816DOI Listing
March 2021

COVID-19-associated coagulopathy: thromboembolism prophylaxis and poor prognosis in ICU.

Exp Hematol Oncol 2021 Feb 1;10(1). Epub 2021 Feb 1.

State Key Lab of Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, China.

Background: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases.

Methods: We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020.

Results: Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality.

Conclusions: A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.
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http://dx.doi.org/10.1186/s40164-021-00202-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848868PMC
February 2021

MC-LR-induced interaction between M2 macrophage and biliary epithelial cell promotes biliary epithelial cell proliferation and migration through regulating STAT3.

Cell Biol Toxicol 2021 Jan 21. Epub 2021 Jan 21.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Hankou Road 22, Nanjing, 210093, Jiangsu, China.

Microcystin-leucine-arginine (MC-LR) was produced by toxic cyanobacteria, which has been shown to have potent hepatotoxicity. Our previous study has proved that MC-LR were able to promote intrahepatic biliary epithelial cell excessive proliferation. However, the underlying mechanism is not yet entirely clarified. Herein, mice were fed with different concentrations (1, 7.5, 15, or 30 μg/L) of MC-LR by drinking water for 6 months. As the concentration of MC-LR increased, a growing number of macrophages were evaluated in the portal area of the mouse liver. Next, we built a co-culture system to explore the interaction between macrophages (THP-1 cells) and human intrahepatic biliary epithelial cells (HiBECs) in the presence of MC-LR. Under the exposure of MC-LR, HiBECs secreted a large amount of inflammatory factors (IL-6, IL-8, IL-1β, COX-2, XCL-1) and chemokine (MCP-1), which produced a huge chemotactic effect on THP-1 cells and induced elevation of the surface M2-subtype biomarkers (IL-10, CD163, CCL22, and Arg-1). In turn, high content of IL-6 in the medium activated JAK2/STAT3, MEK/ERK, and PI3K/AKT pathways in HiBECs, inducing HiBEC abnormal proliferation and migration. Together, these results suggested that MC-LR-mediated interaction between HiBECs and macrophages induced the M2-type polarization of macrophages, and activated IL-6/JAK2/STAT3, MEK/ERK, and PI3K/AKT pathways in HiBECs, further enhanced cell proliferation, improved cell migration, and hindered cell apoptosis by activating p-STAT3. MC-LR stimulates HiBECs to produce various inflammatory factors, recruiting a large number of macrophages and promoting the differentiation of macrophages into M2-type. In turn, the M2 macrophages could also produce amounts of IL-6 and activate STAT3 through JAK2/STAT3, MEK/ERK, and PI3K/AKT pathways in HiBECs, resulting in the promotion of cell proliferation, inhibition of apoptosis, and enhancement of migration.
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http://dx.doi.org/10.1007/s10565-020-09575-9DOI Listing
January 2021

Identification of KRAS mutation in a patient with linear nevus sebaceous syndrome: a case report.

BMC Med Genomics 2020 12 12;13(1):188. Epub 2020 Dec 12.

Department of Dermatologic Surgery, Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, Jiangsu, China.

Background: Linear nevus sebaceous syndrome (LNSS) is a rare genetic disease characterized by large linear sebaceous nevus typically on the face, scalp, or neck. LNSS could be accompanied by multisystem disorders including the central nervous system. Herein, we report gene mutational profile via whole exome sequencing of both lesional and non-lesional skin samples in a LNSS patient.

Case Presentation: A 17-year-old girl presented with multisystem abnormalities, including large skin lesions, ocular disorders, abnormal bone development and neurological symptoms. A diagnosis of LNSS was established based on clinical manifestations, histopathological and imaging findings. The skin lesions were resected and no recurrence was noted at the time of drafting this report. Whole exome sequencing of genomic DNA revealed the following 3 mutations in the lesions of the index patient: KRAS (c.35G > A, p.G12D), PRKRIR (c.A1674T, p.R558S), and RRP7A (c. C670T, p.R224W), but no mutation was found in the healthy skin and peripheral blood sample of the index patient, or in the blood samples of her parents and sibling. PCR-mediated Sanger sequencing of DNA derived from lesional skin sample of the index patient verified KRAS mutation, but not PRKRIR (c.A1674T, p.R558S) and RRP7A (c. C670T, p.R224W). None of the 3 mutations was found in Sanger sequencing in skin lesions of 60 other cases of nevus sebaceous patients.

Conclusions: Our findings show the relevance of KRAS mutation to LNSS, providing new clues in understanding related genetic heterogeneity which could aid genetic counselling for LNSS patients.
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http://dx.doi.org/10.1186/s12920-020-00847-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733249PMC
December 2020

Chronic exposure to microcystin-LR increases the risk of prostate cancer and induces malignant transformation of human prostate epithelial cells.

Chemosphere 2021 Jan 10;263:128295. Epub 2020 Sep 10.

Immunology and Reproduction Biology Laboratory, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China. Electronic address:

Microcystins-LR (MC-LR) acts as a possible carcinogen for humans and causes a serious risk to public environmental health. The current study aimed to evaluate the interaction between MC-LR exposure and prostate cancer development and elucidate the underlying mechanism. In this study, mice were exposed to MC-LR at various doses for 180 days. MC-LR was able to induce the progression of prostatic intraepithelial neoplasia (PIN) and microinvasion. Furthermore, MC-LR notably increased angiogenesis and susceptibility to prostate cancer in vivo. In vitro, over 25 weeks of MC-LR exposure, normal human prostate epithelial (RWPE-1) cells increased secretion of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and colony formation, features typical for cancer cells. These MC-LR-transformed prostate epithelial cells displayed increased expression of forkhead box M1 (FOXM1) and cyclooxygenase-2 (COX-2); abrogation of FOXM1 or COX-2 activity by specific inhibitors could abolish the invasion and migration of MC-LR-treated cells. In conclusion, we have provided compelling evidence demonstrating the induction of a malignant phenotype in human prostate epithelial cells and the in vivo development of prostate cancer by exposure to MC-LR, which might be a potential tumor promoter in the progression of prostate cancer.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128295DOI Listing
January 2021

Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier.

Stem Cells Int 2020 30;2020:8861407. Epub 2020 Oct 30.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.

Mesenchymal stem cells (MSCs) may improve the treatment of acute respiratory distress syndrome (ARDS). However, few studies have investigated the effects of mechanically stretched -MSCs (MS-MSCs) in models of ARDS. The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. We introduced a cocultured model of pulmonary microvascular endothelial cell (EC) and MSC medium obtained from MSCs with or without mechanical stretch. We found that Wright-Giemsa staining revealed that MSC morphology changed significantly and cell plasma shrank separately after mechanical stretch. Cell proliferation of the MS-MSC groups was much lower than the untreated MSC group; expression of cell surface markers did not change significantly. Compared to the medium from untreated MSCs, inflammatory factors elevated statistically in the medium from MS-MSCs. Moreover, the paracellular permeability of endothelial cells treated with LPS was restored with a medium from MS-MSCs, while LPS-induced EC apoptosis decreased. In addition, protective effects on the remodeling of intercellular junctions were observed when compared to LPS-treated endothelial cells. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS.
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http://dx.doi.org/10.1155/2020/8861407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647750PMC
October 2020

The incidence, risk factors and prognosis of acute kidney injury in severe and critically ill patients with COVID-19 in mainland China: a retrospective study.

BMC Pulm Med 2020 Nov 9;20(1):290. Epub 2020 Nov 9.

Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: The clinical correlates, prognosis and determinants of acute kidney injury (AKI) in patients with coronavirus disease 2019 (Covid-19) remain largely unclear.

Methods: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University.

Results: Among 210 patients, 131 were males (62.4%). The median Age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) were classified as being at stage 1, 2 and 3, respectively. 54 patients (58.7%) received continuous renal replacement therapy. Age, sepsis, nephrotoxic drug, invasive mechanical ventilation and elevated baseline serum creatinine levels were associated with the occurrence of AKI. Renal recovery during hospitalization was identified among 16 patients with AKI (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher ratio of partial pressure of oxygen to the fraction of inspired oxygen. Of 210 patients, 93 deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater Age and the lowest ratio of partial pressure of oxygen to the fraction of inspired oxygen being < 150 mmHg were independently associated with death.

Conclusions: Among patients with Covid-19, the incidence of AKI was high. Our findings of the risk factors of the development of AKI and factors associated with renal function recovery may inform clinical management of patients with critical illness of Covid-19.
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http://dx.doi.org/10.1186/s12890-020-01305-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649893PMC
November 2020

Physiological effects of different recruitment maneuvers in a pig model of ARDS.

BMC Anesthesiol 2020 10 21;20(1):266. Epub 2020 Oct 21.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No.87, Dingjiaqiao Road, Gulou District, Nanjing, 210009, Jiangsu, China.

Background: In acute respiratory distress syndrome (ARDS), lung recruitment maneuvers can recruit collapsed alveoli in gravity-dependent lung regions, improving the homogeneity of ventilation distribution. This study used electrical impedance tomography to investigate the physiological effects of different recruitment maneuvers for alveolar recruitment in a pig model of ARDS.

Methods: ARDS was induced in ten healthy male pigs with repeated bronchoalveolar lavage until the ratio of arterial partial pressure of oxygen (PaO) of fraction of inspired oxygen (P/F) was < 100 mmHg and remained stable for 30 min (T). ARDS pigs underwent three sequential recruitment maneuvers, including sustained inflation, increments of positive end-expiratory pressure (PEEP), and pressure-controlled ventilation (PCV) applied in random order, with 30 mins at a PEEP of 5 cmHO between maneuvers. Respiratory mechanics, hemodynamics, arterial blood gas, and electrical impedance tomography were recorded at baseline, T, and before and after each recruitment maneuver.

Results: In all ten pigs, ARDS was successfully induced with a mean 2.8 ± 1.03 L bronchoalveolar lavages. PaO, P/F, and compliance were significantly improved after recruitment with sustained inflation, increments of PEEP or PCV (all p < 0.05), and there were no significant differences between maneuvers. Global inhomogeneity index significantly decreased after recruitment with sustained inflation, increments of PEEP, or PCV. There were no significant differences in global inhomogeneity before or after recruitment with the different maneuvers. The decrease in global inhomogeneity index (ΔGI) was significantly greater after recruitment with increments of PEEP compared to sustained inflation (p = 0.023), but there was no significant difference in ΔGI between increments of PEEP and PCV or between sustained inflation and PCV.

Conclusion: Sustained inflation, increments of PEEP, and PCV increased oxygenation, and regional and global compliance of the respiratory system, and decreased inhomogeneous gas distribution in ARDS pigs. Increments of PEEP significantly improved inhomogeneity of the lung compared to sustained inflation, while there was no difference between increments of PEEP and PCV or between sustained inflation and PCV.
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http://dx.doi.org/10.1186/s12871-020-01164-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576861PMC
October 2020

When dispatcher assistance is not saving lives: assessment of process compliance, barriers and outcomes in out-of-hospital cardiac arrest in a metropolitan city in China.

Emerg Med J 2020 Sep 30. Epub 2020 Sep 30.

Department of Global Health, Peking University School of Public Health, Beijing, China

Background: Several Chinese cities have implemented dispatcher-assisted cardiopulmonary resuscitation (DA-CPR), although out-of-hospital cardiac arrest (OHCA) survival rates remain low. We aimed to assess the process compliance, barriers and outcomes of OHCA in one of the earliest implemented (DA-CPR) programmes in China.

Methods: We retrospectively reviewed OHCA emergency dispatch records of Suzhou emergency medical service from 2014 to 2015 and included adult OHCA victims (>18 years) with a bystander-witnessed atraumatic OHCA that was subsequently confirmed by on-site emergency physician. The circumstances and DA-CPR process related to the OHCA event were analysed. Dispatch audio records were reviewed to identify potential barriers to implementation during the DA-CPR process.

Results: Of the 151 OHCA victims, none survived. The median time from patient collapse to call for emergency services and that from call to provision of cardiopulmonary resuscitation instructions was 30 (IQR 20-60) min and 115 (IQR 90-153) s, respectively. Only 110 (80.3%) bystanders/rescuers followed the dispatcher instructions; of these, 51 (46.3%) undertook persistent chest compressions. Major barriers to following the DA-CPR instructions were present in 104 (68.9%) cases, including caller disconnection of the call, distraught mood or refusal to carry out either compressions or ventilations.

Conclusions: The OHCA survival rate and the DA-CPR process were far from optimal. The zero survival rate is disproportionally low compared with survival statistics in high-income countries. The prolonged delay in calling the emergency services negated and rendered futile any DA-CPR efforts. Thus, efforts targeted at developing public awareness of OHCA, calling for help and competency in DA-CPR should be increased.
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http://dx.doi.org/10.1136/emermed-2019-209291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982934PMC
September 2020

Pretreatment with human urine-derived stem cells protects neurological function in rats following cardiopulmonary resuscitation after cardiac arrest.

Exp Ther Med 2020 Nov 18;20(5):112. Epub 2020 Sep 18.

Dispatch Department, Suzhou Emergency Center, Suzhou, Jiangsu 215000, P.R. China.

Cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) often leads to neurological deficits in the absence of effective treatment. The aim of the present basic research study was to investigate the effects of human urine-derived stem cells (hUSCs) on the recovery of neurological function in rats after CA/CPR. hUSCs were isolated and identified using flow cytometry. A rat model of CA was established, and CPR was performed. Animals were scored for neurofunctional deficits following hUSC transplantation. The expression levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the hippocampus and temporal cortex were detected via immunofluorescence. Moreover, brain water content and serum S100 calcium binding protein B (S100B) levels were measured 7 days following hUSC transplantation. The results demonstrated that hUSCs had upregulated expression levels of CD29, CD90, CD44, CD105, CD73, CD224 and CD146, and expressed low levels of CD34 and human leukocyte antigen-DR isotype. In addition, hUSCs were able to differentiate into neuronal cells . The SPSS 19.0 statistical package was used for statistical analysis, and it was found that the neurological function of the rats after CA/CPR was significantly improved following hUSC transplantation. Furthermore, hUSCs aggregated in the hippocampus and temporal cortex, and secreted large amounts of BDNF and VEGF. hUSC transplantation also effectively inhibited brain edema and serum S100B levels after CPR. Therefore, the results suggested that hUSC transplantation significantly improved the neurological function of rats after CA/CPR, possibly by promoting the expression levels of BDNF and VEGF, as well as inhibiting brain edema.
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http://dx.doi.org/10.3892/etm.2020.9240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517276PMC
November 2020

Long non-coding RNA Hsp4 alleviates lipopolysaccharide-induced apoptosis of lung epithelial cells via miRNA-466m-3p/DNAjb6 axis.

Exp Mol Pathol 2020 12 23;117:104547. Epub 2020 Sep 23.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address:

Acute lung injury (ALI), as a life-threatening syndrome, is mainly characterized with diffuse alveolar injury, excessive pulmonary inflammation, edema and apoptosis of lung epithelial cells. This study investigated the effects of LncRNA Hsp4 (Hsp4, ENSMUST00000175718) on lipopolysaccharide (LPS)-induced apoptosis of MLE-12 cells. In our research, we found that LPS treatment remarkably induced apoptosis of MLE-12 cells and decreased the expression of Hsp4. Overexpression of Hsp4 significantly reversed LPS-induced cell apoptosis through inhibiting mTOR signaling, while suppression of Hsp4 presented opposite effects. Further results showed that Hsp4 positively regulated the expression of miR-466m-3p. Knockdown of miR-466m-3p reversed LPS-induced cell apoptosis via increasing the levels of DNAjb6 which was confirmed to be the target gene of miR-466m-3p. This finding will be helpful for further understanding the critical roles of Hsp4 in ALI and may provide potential targets for ALI diagnosis and treatment.
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http://dx.doi.org/10.1016/j.yexmp.2020.104547DOI Listing
December 2020

Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study.

Intensive Care Med 2020 10 20;46(10):1863-1872. Epub 2020 Aug 20.

Medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Purpose: An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality.

Methods: We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors.

Results: Of the 733 patients included in the study, the median (IQR) age was 65 (56-73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high D-dimer level, low PaO/FiO level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19.

Conclusion: In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources.
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http://dx.doi.org/10.1007/s00134-020-06211-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439240PMC
October 2020

Reply by Pan to Haouzi

Am J Respir Crit Care Med 2020 08;202(4):630-631

Zhongda HospitalNanjing, China.

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http://dx.doi.org/10.1164/rccm.202005-2045LEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427396PMC
August 2020

Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan, China.

Ann Intensive Care 2020 Jun 6;10(1):73. Epub 2020 Jun 6.

Department of Critical Care Medicine, Shanghai Jiaotong University, School of Medicine, Ruijin Hospital North, No. 197 Ruijin 2nd Road, Huangpu District, Shanghai, 201801, China.

Background: The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed.

Methods: Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences.

Results: A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts' opinions. A strong agreement from voting participants was obtained for all recommendations.

Conclusion: There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.
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http://dx.doi.org/10.1186/s13613-020-00689-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275657PMC
June 2020

The mechanisms in the altered ontogenetic development and lung-related pathology in microcystin-leucine arginine (MC-LR)-paternal-exposed offspring mice.

Sci Total Environ 2020 Sep 25;736:139678. Epub 2020 May 25.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China. Electronic address:

A father's lifetime experience is a major risk factor for a range of diseases in an individual, and the consequences of the exposure can also be transmitted to his offspring. Our previous work has demonstrated that damage to testicular structures and decline in sperm quality in male mice can be caused by microcystin-leucine arginine (MC-LR), but the overall effects of the scope and extent of paternal exposure on health and disease in the offspring remain underexplored. Here, we report that MC-LR-paternal-exposed offspring mice showed reduced litter size and body weight accompanied by increased abnormalities in the lung. Analyses of the small noncoding RNAs (sncRNAs) in the sperm from MC-LR-exposed males demonstrated the downregulation of a wide range of piRNAs enriched for those target genes involved in the regulation of the embryo implantation pathways. Gene and protein expression analyses, as well as biochemical and functional studies, revealed suppressed expression of Hsp90α in testicular tissues from MC-LR-exposed males. Decreased Hsp90α in testicular tissues impaired the development of the offspring. In this study, we revealed that MC-LR alters the expression of Hsp90α in testicular tissues to cause changes in the expression profiles of sperm piRNAs produced by paternal mice. These changes lead to aberrant activation of the Wnt/β-catenin signaling pathway in pulmonary tissues of offspring mice, causing lung tissue damage and abnormal development. We hereby confirmed that MC-LR-induced alterations in epigenetic inheritance are capable of contributing to intergenerational developmental defects in paternal-exposed offspring mice.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139678DOI Listing
September 2020

A Bayesian approach for analyzing partly interval-censored data under the proportional hazards model.

Stat Methods Med Res 2020 11 22;29(11):3192-3204. Epub 2020 May 22.

Department of Statistics, University of South Carolina, Columbia, SC, USA.

Partly interval-censored time-to-event data often occur in biomedical studies of diseases where periodic medical examinations for symptoms of interest are necessary. Recent decades have seen blooming methods and R packages for interval-censored data; however, the research effort for partly interval-censored data is limited. We propose an efficient and easy-to-implement Bayesian semiparametric method for analyzing partly interval-censored data under the proportional hazards model. Two simulation studies are conducted to compare the performance of the proposed method with two main Bayesian methods currently available in the literature and the classic Cox proportional hazards model. The proposed method is applied to a partly interval-censored progression-free survival data from a metastatic colorectal cancer trial.
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http://dx.doi.org/10.1177/0962280220921552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592883PMC
November 2020

Optimal mean airway pressure during high-frequency oscillatory ventilation in an experimental model of acute respiratory distress syndrome: EIT-based method.

Ann Intensive Care 2020 Mar 6;10(1):31. Epub 2020 Mar 6.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Jiangsu Province, Nanjing, 210009, China.

Background: High-frequency oscillatory ventilation (HFOV) may theoretically provide lung protective ventilation. The negative clinical results may be due to inadequate mean airway pressure (mPaw) settings in HFOV. Our objective was to evaluate the air distribution, ventilatory and hemodynamic effects of individual mPaw titration during HFOV in ARDS animal based on oxygenation and electrical impedance tomography (EIT).

Methods: ARDS was introduced with repeated bronchoalveolar lavage followed by injurious mechanical ventilation in ten healthy male pigs (51.2 ± 1.9 kg). Settings of HFOV were 9 Hz (respiratory frequency), 33% (inspiratory time) and 70 cmHO (∆pressure). After lung recruitment, the mPaw was reduced in steps of 3 cmHO every 6 min. Hemodynamics and blood gases were obtained in each step. Regional ventilation distribution was determined with EIT.

Results: PaO/FiO decreased significantly during the mPaw decremental phase (p < 0.001). Lung overdistended regions decreased, while recruitable regions increased as mPaw decreased. The optimal mPaw with respect to PaO/FiO was 21 (18.0-21.0) cmHO, that is comparable to EIT-based center of ventilation (EIT-CoV) and EIT-collapse/over, 19.5 (15.0-21.0) and 19.5 (18.0-21.8), respectively (p = 0.07). EIT-CoV decreasing along with mPaw decrease revealed redistribution toward non-dependent regions. The individual mPaw titrated by EIT-based indices improved regional ventilation distribution with respect to overdistension and collapse (p = 0.035).

Conclusion: Our data suggested personalized optimal mPaw titration by EIT-based indices improves regional ventilation distribution and lung homogeneity during high-frequency oscillatory ventilation.
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http://dx.doi.org/10.1186/s13613-020-0647-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060304PMC
March 2020

Safety and efficacy of nazartinib (EGF816) in adults with EGFR-mutant non-small-cell lung carcinoma: a multicentre, open-label, phase 1 study.

Lancet Respir Med 2020 06 15;8(6):561-572. Epub 2020 Jan 15.

Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.

Background: Resistance to first-generation and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is mediated by the emergence of the Thr790Met mutation in 50-60% of treated patients with non-small-cell lung cancer (NSCLC). We aimed to assess the safety and activity of nazartinib (EGF816), a third-generation EGFR TKI that selectively inhibits EGFR with Thr790Met or activating mutations (or both), while sparing wild-type EGFR, in patients with advanced EGFR-mutant NSCLC.

Methods: This phase 1 dose-escalation part of an open-label, multicentre, phase 1/2 study was conducted at nine academic medical centres located in Europe, Asia, and North America. Patients were included if they were aged 18 years or older and had stage IIIB-IV EGFR-mutant NSCLC (with varying statuses of EGFR mutation and previous therapy allowed), at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Nazartinib (at seven dose levels between 75 mg and 350 mg, in capsule or tablet form) was administered orally, once daily, on a continuous 28-day dosing schedule. A two-parameter Bayesian logistic regression model, guided by the escalation with overdose control principle, was implemented to make dose recommendations and estimate the maximum tolerated dose or recommended phase 2 dose of nazartinib (the primary outcome). This study is registered with ClinicalTrials.gov (NCT02108964); enrolment to phase 1 is complete and the study is ongoing.

Findings: By Aug 31, 2017, 180 patients (116 [64%] women; median age 60 years (52-69); 116 [64%] with ECOG performance status 1) received nazartinib across seven dose levels: 75 mg (n=17), 100 mg (n=38), 150 mg (n=73), 200 mg (n=8), 225 mg (n=28), 300 mg (n=5), and 350 mg (n=11). Seven dose-limiting toxicities were observed in six (3%) patients who received 150 mg, 225 mg, or 350 mg nazartinib once daily. Although the maximum tolerated dose was not met, the recommended phase 2 dose was declared as 150 mg once daily (tablet). The most common adverse events, regardless of cause, were rash (all subcategories 111 [62%] patients, maculopapular rash 72 [40%], dermatitis acneiform 22 [12%]), diarrhoea (81 [45%]), pruritus (70 [39%]), fatigue (54 [30%]), and stomatitis (54 [30%]), and were mostly grades 1-2. Any-cause grade 3-4 adverse events were reported in 99 (55%) patients across all doses, the most common being rash (all subcategories grouped 27 [15%]), pneumonia (12 [7%]), anaemia (ten [6%]), and dyspnoea (nine [5%]). Serious adverse events suspected to be drug-related occurred in 16 (9%) patients.

Interpretation: Nazartinib has a favourable safety profile, with low-grade skin toxicity characterised by a predominantly maculopapular rash that required minimal dose reductions.

Funding: Novartis Pharmaceuticals Corporation.
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http://dx.doi.org/10.1016/S2213-2600(19)30267-XDOI Listing
June 2020

piR-31470 epigenetically suppresses the expression of glutathione S-transferase pi 1 in prostate cancer via DNA methylation.

Cell Signal 2020 03 16;67:109501. Epub 2019 Dec 16.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China. Electronic address:

Inactivation of glutathione S-transferase pi 1 (GSTP1) via hypermethylation is an early and common event in prostate carcinogenesis. Functional inactivation of GSTP1 increases the susceptibility to oxidative stress and enhance progression risk of the prostatic carcinoma. In this study, we hypothesized that the Piwi-interacting RNA (piRNA) could be a sequence-recognition and guidance molecule for induction of promoter methylation of GSTP1 facilitating prostate carcinogenesis. We found that piR-31470 was highly expressed in prostate cancer cells, and piR-31470 could bind to piwi-like RNA-mediated gene silencing 4 (PIWIL4) to form the PIWIL4/piR-31470 complex. This complex could bind to the nascent RNA transcripts of GSTP1, and recruit DNA methyltransferase 1, DNA methyltransferase 3 alpha and methyl-CpG binding domain protein 2 to initiate and maintain the hypermethylation and inactivation of GSTP1. Our data demonstrated that the overexpression of piR-31470 inhibited the levels of GSTP1 and increased vulnerability to oxidative stress and DNA damage in human prostate epithelial RWPE1 cells. In conclusion, this study characterized the roles of the PIWIL4/piR-31470 complex in the regulation of the transcription of GSTP1 by methylating the CpG island of GSTP1. This discovery may provide a novel therapeutic strategy by targeting piRNAs for the epigenetic treatment of prostate cancer.
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http://dx.doi.org/10.1016/j.cellsig.2019.109501DOI Listing
March 2020

Reply to: Why would procalcitonin perform better in patients with a SOFA-score less than 8?

Int J Infect Dis 2019 12 3;89:187-188. Epub 2019 Oct 3.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing 210009, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.ijid.2019.09.026DOI Listing
December 2019

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study.

Chin Med J (Engl) 2019 Sep;132(18):2192-2198

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.

Background: Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS.

Methods: We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality.

Results: Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ± 6.3 in the ECMO group and 24.8 ± 8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ± 3.4 in the ECMO group and 13.7 ± 3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001-1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264-8.609; P = 0.034).

Conclusions: This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.
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http://dx.doi.org/10.1097/CM9.0000000000000424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797139PMC
September 2019

Cutaneous Tuberculosis and Nontuberculous Mycobacterial Infections at a National Specialized Hospital in China.

Acta Derm Venereol 2019 Oct;99(11):997-1003

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 210042 Nanjing, China.

To identify the microorganism distribution clinical characteristics and management of cutaneous Mycobacterium tuberculosis and nontuberculous mycobacterial infectious diseases in the past 10 years we collected and analyzed the patient records of all cutaneous M. tuberculosis and nontuberculous mycobacterial infection cases diagnosed by culture and/or PCR from 2008 to 2017 in the Hospital of Dermatology Chinese Academy of Medical Sciences. Among 203 cases including 89 M. tuberculosis infections and 114 nontuberculous mycobacterial infections M. tuberculosis was the most common species in all patients and M. marinum predominated among the nontuberculous mycobacterial followed by M. abscessus. Cases of cutaneous mycobacterial infection especially nontuberculous mycobacterial infection increased in the past 10 years and infection with rapidly growing mycobacteria significantly increased in the last 5 years in this national hospital in Southeast China. Injuries were common causative factors. Approximately 91.3% of patients responded well to longstanding antibiotic therapy.
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http://dx.doi.org/10.2340/00015555-3283DOI Listing
October 2019

[Heiguteng Zhuifenghuoluo capsule inhibits the expression of NF-κB in synovial tissues of rats with collagen-induced arthritis and alleviates joint inflammation].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Mar;35(3):193-198

Guizhou University of Chinese Medicine, Guiyang 550025, China. *Corresponding author, E-mail:

Objective To investigate the effect of Heiguteng Zhuifenghuoluo Capsule (HZC) on nuclear factor kappa B (NF-κB)-related protein in rheumatoid arthritis rats, and to analyze the expression of IκBα, NF-κBp65, phospho-nuclear factor kappa B p65 (p-NF-κBp65), receptor activator of nuclear factor κB ligand (RANKL), transforming growth factor activated kinase 1(TAK1), transforming growth factor β activated kinase binding protein 1(TAB1), monocyte chemoattractant protein 1 (MCP-1), C-X-C motif chemokine ligand 1 (CXCL1), macrophage inflammatory protein-1 (MIP-1) of plasma in rheumatoid arthritis rats. Methods Male SD rats were randomly divided into control group, model group, HZC (0.315 g/kg) group, and HZC (0.315 g/kg) plus ammonium pyrrolidinedithiocarbamate (PDTC, 0.01 g/kg) group. The model was constructed in all groups except the control group. Five weeks after modeling, the plantar thickness and spleen organ coefficient (spleen/body weight ratio) were measured in all rats. The TAK1 and TAB1 proteins were detected by immunohistochemical method in the spleen. Western blot analysis was used to detect the expression of IκBα, NF-κBp65, p-NF-κBp65 and RANKL proteins in the synovium of joint and plantar tissue. MCP-1, CXCL1, MIP-1 expression in the plasma was detected by ELISA. Results Compared with the model group, the swelling degree of plantar and the spleen organ coefficient in the control group, HZC group and combined administration group decreased significantly. The immunohistochemistry showed that the expression of TAK1 and TAB1 proteins in the spleen were down-regulated in the control group, HZC group and combined administration group. Western blotting showed that the expression of IκBα protein was up-regulated in the synovium of joint tissue of the control group, HZC group and combined administration group, but the expression of NF-κBp65, p-NF-κBp65, RANKL proteins were down-regulated in the control group, HZC group and combined administration group. ELISA showed that the expression of plasma MCP-1, CXCL1, MIP-1 were down-regulated in the control group, HZC group and combined administration group. Conclusion HZC inhibits the inflammatory response of rheumatoid arthritis rats by regulating NF-κB-related proteins.
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March 2019

Structural characterization and rheological properties of a pectin with anti-constipation activity from the roots of Arctium lappa L.

Carbohydr Polym 2019 Jul 20;215:119-129. Epub 2019 Mar 20.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

A new pectin (ALP-2) was extracted from the roots of Arctium lappa L. with the molecular weight of 1.84 × 10 Da. ALP-2 was composed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose and arabinose. Results of NMR revealed that the dominant linkage types of ALP-2 were →4-α-GalpA-6-OMe-(1→, →2-α-Rha-(1→, →5-α-Araf-(1→ and →3,6-β-Galp-(1→. The ELISA results indicated ALP-2 was a typical pectin with HG chain and RG-I chain. The rheological experiments showed that ALP-2 fluid exhibited shear thinning behavior. The viscosity of ALP-2 was mainly affected by concentration, temperature, and pH. The ALP-2 fluid with elastic properties at high frequencies could be used as a thickener in the food industry. Moreover, ALP-2 with the dosages of 200 mg/kg and 400 mg/kg exhibited strong anti-constipation activity in vivo. ALP-2 treated groups could improve small intestinal movement rate and increase the weight of feces significantly in constipation mice. Therefore, ALP-2 could be considered as the active component for functional food or therapeutic agent in constipation therapy.
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http://dx.doi.org/10.1016/j.carbpol.2019.03.051DOI Listing
July 2019

Chemical and rheological properties of proteoglycans from Sarcandra glabra (Thunb.) Nakai.

Int J Biol Macromol 2019 Jul 30;132:641-650. Epub 2019 Mar 30.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Two proteoglycans (HPP and LPP) with different ratios of protein/polysaccharide were extracted from S. glabra. The chemical compositions, relative average molecular weights, monosaccharide compositions, FT-IR spectra, and rheological properties of the two proteoglycans were determined. The results exhibited that the two proteoglycans had pseudoplastic fluids properties and displayed shear-thinning behavior. The apparent viscosity of the two proteoglycans both increased with increasing concentrations. The temperature had different effects on the viscosity of the two proteoglycans. As temperature increased from 25 to 85 °C, the viscosity of LPP descended while the HPP's viscosity rose first and then dropped slightly. The effects of CaCl addition on the two samples were like that of the temperature. The viscosities of HPP and LPP had different tolerances to acidity and alkalinity. HPP solution was more sensitive to pH changes due to its high protein content. The addition of sucrose increased the viscosities of samples. The modulus G' and G″ of HPP and LPP were increased with the increase of oscillation frequency, while the crossover points of G' and G″ values decreased with the increasing concentrations of HPP and LPP. The above data presented that the two proteoglycans could be promising candidates for food industries and pharmacological applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.03.228DOI Listing
July 2019
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