Application Efficacy of Cluster Nursing in Patients Undergoing Gastrointestinal Endoscopy.

Background: Gastrointestinal endoscopy is a clinical examination of gastrointestinal diseases with pain, nausea, and other discomfort of the patient. Therefore, it is of practical significance to give corresponding nursing intervention for patients undergoing painless gastrointestinal endoscopy. Objective: To probe the application efficacy of cluster nursing in patients undergoing gastrointestinal endoscopy. Design: This was a retrospective study. Setting: This study was carried out in the Department of Endoscopy Room, Funan County Hospital of Traditional Chinese Medicine. Participants: From March 2020 to October 2022, 126 patients who underwent painless gastrointestinal endoscopy were chosen and randomly separated into a control group and research group. Interventions: The control group received routine safety nursing management. The research group adopted safety management guided by a cluster nursing strategy. Primary Outcome Measures: (1) the dosage of anesthetic drug use and examination time (2) hemodynamics (3) occurrence of common adverse events (4) score of bowel preparation (5) scores of anxiety and depression (6) comfort degree and (7) nursing satisfaction. Results: Compared to the control group, the dosage of anesthetic drug use and examination time in the research group were lessened (P < .001, 95% CI: -10.06--7.94 and P < .001, 95% CI: -7.10--4.88), the diastolic blood pressure, systolic blood pressure, and heart rate indexes in the research group were reduced (P = .03, 95% CI:-10.07--5.32; P < .001, 95% CI:-13.87--7.91 and P < .001, 95% CI:-12.23--6.27), the occurrence of adverse events during the examination in the research group was reduced (χ2=8.068, P = .005), the score of bowel preparation in the research group was elevated (P < .001, 95% CI: 1.06-1.56), the scores of anxiety as well as depression in the research group were reduced (P < .001, 95% CI: 10.77-13.35 and P < .001, 95% CI: 7.31-9.53), the comfort score of patients in the research group presented higher (P < .001, 95% CI: 17.77-22.91), and the nursing satisfaction in the research group was elevated (χ2=10.31, P = .001). Conclusion: Cluster nursing for patients with painless gastrointestinal endoscopy combined examination has a positive impact on ensuring the successful completion of the examination, effectively controlling the risk of adverse events, and improving patient satisfaction.

[Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023)].

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.

Family Supportive Leadership and Counterproductive Work Behavior: The Roles of Work-Family Conflict, Moral Disengagement and Personal Life Attribution.

Counterproductive work behavior (CWB) is one of the most common behavioral decisions of employees in the workplace that negatively impacts the sustainable development of enterprises. Previous studies have shown that individuals make CWB decisions for different reasons. Some individuals engage in CWB due to cognitive factors (i.e., perceived organizational justice and psychological contract breakdown), whereas others engage in CWB in response to leadership behaviors (i.e., abusive management). The conservation of resources (COR) theory holds that individuals have the tendency to preserve, protect and acquire resources. When experiencing the loss of resources, individuals will show irrational and aggressive behaviors in order to regain resources. When obtaining resources, individuals' tension and pressure will be relieved. To maintain or continue obtaining resources, individuals will show more positive work attitudes and behaviors. Therefore, using the COR theory as the main theoretical framework, this study explores a serial mediation model between family supportive leadership and CWB through work-family conflict and moral disengagement, moderated by personal life attribution. A three-wave survey of 251 medical workers from three hospitals found that family supportive leadership can reduce employees' perceived work-family conflict, which leads to less moral disengagement, resulting in lower CWB. Personal life attribution strengthens the negative indirect effect of family supportive leadership on CWB by reinforcing the negative association between family supportive leadership and work-family conflict. This study uses the COR theory to explore the mechanism and boundary conditions of family supportive leadership and CWB from the perspective of negative work-family relationship, which enrichis the research content of existing theories. Moreover, this study has important guiding significance for managers to take effective measures to reduce CWB.

Dynamic role of macrophage CX3CR1 expression in inflammatory bowel disease.

Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), is featured by overactive immune response and enduring course of unrestrained colitis. Genetic predisposition and environmental factors are fundamental in disease progression. Notably, microbiota dysregulation and its interaction with host mucosal barrier perplex disease phenotype. Under experimental setting, distinct mouse models are established to mimic human colitis process, including infection induced dysbiosis, dextran sulfate sodium (DSS) etc. induced barrier destruction, anti-CD40 L induced innate immunity dominant colitis and T cell transfer colitis model. Thus, from a more detailed aspect, IBD is heterogeneous and can be further classified into different subtypes based on the specific etiological pathways. As a typical inflammatory disorder, various immune cell types are involved in IBD pathogenesis. Among them, macrophages are believed to play a pivotal role. CX3CR1+ macrophages, deriving from peripheral patrolling CD14+ Ly6Chi monocytes, are specified cell population dwelling in the gut. Accumulating evidence suggests that CX3CR1+ macrophages are critical for mucosal homeostasis and IBD pathogenesis, while some conflicts exist in current studies with both protective and harmful effects being revealed. Herein, we reviewed published literatures and found that the observed discrepancies stem from many aspects: the expression level of CX3CR1, the confounding dendritic cell subsets and most importantly, the different colitis stages and subtypes. Overall, CX3CR1 targeting strategy could be powerful weapon in fighting against colitis, but at the same time, the precise etiological and pathological mechanisms should be cautiously examined concerning the appropriate usage of CX3CR1 targeted therapy.

Osteopontin Regulates Endometrial Stromal Cell Migration in Endometriosis through the PI3K Pathway : Osteopontin Regulates Endometrial Cell Migration in Endometriosis.

Endometriosis is generally characterized as a tumor-like disease because of its potential for distant metastasis and local tissue invasion, while whether osteopontin (OPN) plays a role in the pathogenesis of endometriosis has not been thoroughly investigated. We investigated the expression of OPN, urokinase plasminogen activator (uPA), phosphatidylinositol 3 kinase (PI3K), and phospho-PI3 kinase (p-PI3K) in endometrial stromal cells (ESCs). The serum concentration of OPN was determined by enzyme-linked immunosorbent assays (ELISA). OPN was downregulated to explore the corresponding change of uPA, p-PI3K, F-actin, and α-tubulin. The expression of OPN, uPA, PI3K, and p-PI3K was evaluated by western blot and quantitative real-time PCR (RT-qPCR) and the expression of F-actin and α-tubulin was confirmed by immunofluorescence assay. The proliferation and migration abilities of ESCs were investigated by CCK8, transwell, and wound scratch assays. Endometrial OPN, p-PI3K, and uPA expressions and serum OPN levels were increased in patients with endometriosis compared with the control. The expressions of p-PI3K, uPA, and α-tubulin were decreased by siRNA-OPN interference in ectopic ESCs. Activation and inhibition of the PI3K pathway apparently upregulate and downregulate uPA expression. Knockdown of OPN and inhibition of the PI3K pathway remarkably inhibited cell migration in ectopic ESCs. Meanwhile, activation of the PI3K pathway promoted the migration ability of ectopic ESCs. OPN may regulate the expression of uPA through the PI3K signal pathway to affect the migration ability of ESCs, indicating that OPN, uPA, and the PI3K pathway may be potential targets for interrupting development of endometriosis.

CT-derived abdominal adiposity: Distributions and better predictive ability than BMI in a nationwide study of 59,429 adults in China.

BACKGROUND: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population. METHOD: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained. RESULTS: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ±â€¯3.0 kg/m2, 90 ±â€¯8 cm, 194 ±â€¯77 cm2, 85 ±â€¯41 cm2, and 69.5 ±â€¯9.1%, respectively, in men and 23.3 ±â€¯3.1 kg/m2, 79 ±â€¯8 cm, 120 ±â€¯57 cm2, 123 ±â€¯53 cm2, and 48.9 ±â€¯9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm2 (95% confidence interval [CI]: 41 cm2, 50 cm2) higher in men and 43 cm2 (95% CI: 37 cm2, 49 cm2) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group. CONCLUSION: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population.

Opportunistic Screening Using Low-Dose CT and the Prevalence of Osteoporosis in China: A Nationwide, Multicenter Study.

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1 -L2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3 ) than men (176.6 mg/cm3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3 ) than men (92.1 mg/cm3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

The study protocol for the China Health Big Data (China Biobank) project.

BACKGROUND: Osteoporosis, obesity, and fatty liver are increasingly common chronic diseases that seriously threaten people's health. Low-dose chest computed tomography (LDCT) scan is frequently used for lung cancer screening in health screenings and checkups. Quantitative computed tomography (QCT) enables the accurate measurement of volumetric bone mineral density (vBMD), liver fat content, and abdominal fat area using the existing LDCT data without extra radiation. We initiated a new project, the China Health Big Data (China Biobank), which combines the LDCT scan images from lung cancer screening of participants in health checkup with QCT to investigate the added value of QCT to LDCT, in order to establish the normative reference database and diagnosis criteria for the three aforementioned conditions. METHODS: The China Biobank project is a prospective nationwide multicenter cohort study that will combine QCT technology with LDCT scans to measure bone mineral density (BMD), intra-abdominal fat distribution, and liver fat content of the generally healthy checkup participants. Mindways QCT calibration phantom (Mindways Software Inc., Austin, TX, USA) and analysis software QCT PRO v6.0 will be used for all centers. Before data collection begins, the European Spine Phantom (ESP) will be used for quality control analysis at each collaborating center. The inclusion criteria are a healthy checkup participant aged 30-90 years, with LDCT as a part of his/her health checkup protocol. Exclusion criteria are pregnant women or participants with a metal implant in the CT scan area. The LDCT images will be transferred to the Mindways workstation for analysis, and vBMD in the L1 and L2 vertebrae, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat content will be measured. As part of the health checkup, the demographic, anthropometric parameters, blood pressure, and a routine blood laboratory test will be collected. The estimated sample size will be about 30,000. RESULTS: The combination of QCT with LDCT of the chest was validated in this project. The vBMD of spine, visceral fat and liver fat can be measured with a LDCT chest scan. CONCLUSIONS: The China Biobank project will assess the added value of QCT to LDCT, and enable accurate evaluation of the prevalence of osteoporosis, obesity, and fatty liver disease in a very large Chinese cohort.

The Prevalence of Osteoporosis in China, a Nationwide, Multicenter DXA Survey.

A number of studies investigated the distribution of BMD values and the prevalence of osteoporosis in China, but their findings varied. Until now, a BMD reference database based on uniform measurements in a large-scale Chinese population has been lacking. A total of 75,321 Chinese adults aged 20 years and older were recruited from seven centers between 2008 and 2018. BMD values at the lumbar spine (L1 -L4 ), femoral neck, and total femur were measured by GE Lunar dual-energy X-ray absorptiometry systems. BMD values measured in each center were cross-calibrated by regression equations that were generated by scanning the same European spine phantom 10 times at every center. Cubic and multivariate linear regression were performed to assess associations between BMD values and demographic variables. Sex-specific prevalence of osteoporosis was age-standardized based on the year 2010 national census data for the Chinese population. The sex-specific BMD values at each site were negatively associated with age, positively associated with body mass index levels, and lower in the participants from southwest China than in those from other geographic regions after multivariate adjustment. Furthermore, BMD values at the femoral neck and total femur decreased with the year of BMD measurement. The peak BMD values at the lumbar spine, femoral neck, and total femur were 1.088 g/cm2 , 0.966 g/cm2 , and 0.973 g/cm2 , respectively, for men, and 1.114 g/cm2 , 0.843 g/cm2 , and 0.884 g/cm2 , respectively, for women. The age-standardized prevalence of osteoporosis at the spine or hip was 6.46% and 29.13% for men and women aged 50 years and older, respectively. Currently a total of 10.9 million men and 49.3 million women in China are estimated to have osteoporosis. In our national examination of BMD, we found that BMD values differed by demographic characteristics. We estimated the age-standardize prevalence of osteoporosis in China to be 6.46% and 29.13% respectively, for men and women aged 50 years and older.

H3K4 Methylation Regulates LPS-Induced Proinflammatory Cytokine Expression and Release in Macrophages.

Histone methylation is an important epigenetic mechanism that plays an essential role in regulating gene expression in mammalian cells. To understand its influence on inflammation, methylation of H3K4, H3K9, H3K36, H3K79, and H4K20, the most common histones methylated in the inflammatory response was analyzed in murine RAW264.7 cells and bone marrow-derived macrophages (BMDMs) upon lipopolysaccharide (LPS) stimulation. LPS stimulation resulted in enhanced methylation at H3K4 and H3K9 in both RAW264.7 and BMDMs. To further confirm whether LPS-stimulated H3K4me2 and H3K9me2 were responsible for subsequent proinflammatory cytokine expression, the recruitment of H3K4me2 and H3K9me2 at the promoters of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) was assessed. H3K4me2, but not H3K9me2, was enriched at the promoters of both IL-6 and TNF-α. Furthermore, LPS-stimulated gene expression and release of IL-6 and TNF-α were markedly suppressed in macrophages by MTA, a specific inhibitor of H3K4 methylation. These results demonstrate that histone methylation, in particular H3K4me2, plays a critical role in the regulation of LPS-induced expression and release of IL-6 and TNF-α.

Polychlorinated biphenyl 104 promotes migration of endometrial stromal cells in endometriosis.

Polychlorinated biphenyls (PCBs), as part of environmental contaminants, have been proved to be related to endometriosis. This study is to investigate the effect of PCB 104 on cell migration, invasion and resultant gene expression in endometrial stromal cells (ESCs). Fifty-three specimens of eutopic endometrial tissues were collected from twenty-four women with endometriosis (EU-EMS) and twenty-nine women without endometriosis (EU-NON). Both EU-EMS and EU-NON were divided into the PCB 104 exposure group and the control group according to whether they were exposed to PCB 104. Primary cultured ESCs were exposed to PCB 104 at the micro molar doses (2 × 10-3, 0.2 and 1 µmol/L) and concentrations of 2, 5 and 10 µmol/L in six-well plates. Cell mobility and proliferation assay were used to evaluate the effects of PCB 104 on the migration, invasion and proliferation of ESCs, and the effect of PCB 104 on actin cytoskeleton was also examined by immunofluorescence. Subsequently, the mRNA levels of related genes including matrix metalloproteinase (MMP) -2, -3, -9, -10, E-cadherin, Snail, Slug and tissue inhibitor of metalloproteinase (TIMP) -2 in ESCs were examined by using real-time PCR, as well as protein levels of MMP-3 and MMP-10 were detected by enzyme-linked immunosorbent assay (ELISA). We explored the role of epidermal growth factor receptor (EGFR) in the expression of MMP-3 and MMP-10 induced by PCB 104. Exposure to PCB 104 significantly increased the migration and invasion of ESCs. The mRNA and protein levels of MMP-3 and MMP-10 in ESCs treated with PCB 104 were higher than that in the control, with a dose- and time-dependent manner in mRNA level, while the expression of MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not change significantly. Taken together, PCB 104 promotes migration and invasion of ESCs by inducing the expression of MMP-3 and MMP-10, which may involved the EGFR signalling pathway.

A novel INDEL mutation in the PTCH1 gene in a Chinese family with Gorlin syndrome.

Gorlin syndrome is a rare autosomal dominant disorder, and 50% of the cases are due to the mutation of PTCH1, the major receptor of the hedgehog signaling pathway. Here we report a new Gorlin syndrome family found in Xinzhou, China. A further sequence analysis found a novel PTCH1 INDEL mutation, NM_001083602.2: c.1516_1524delinsTGAGCTGGAGCTCCG (p. Ala506*), leading an N Terminal truncated protein. This truncated PTCH1 was considered as non-functional version as it loses almost all functional domains, including the 4-12 transmembrane domains and the intracellular and extracellular domains accordingly. Although the effect of the N-terminal truncated PTCH1 is not clear, Gorlin syndrome in these cases is due to haploinsufficiency. Our report enriches the Gorlin syndrome database and will help to unveil the molecular basis of this condition.

Aloperine Protects Mice against DSS-Induced Colitis by PP2A-Mediated PI3K/Akt/mTOR Signaling Suppression.

Colitis is a major form of inflammatory bowel disease which involved mucosal immune dysfunction. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases. The present study aimed to examine the molecular mechanisms underlying aloperine-mediated colitis protection. We found that aloperine treatment improved colitis induced by dextran sodium sulfate (DSS) based on body weight, disease activity index, colonic length, and spleen index. Aloperine also effectively attenuated DSS-induced intestinal inflammation based on the pathological score and myeloperoxidase expression and activity in colon tissues. In addition, aloperine regulated T-cell proportions and promoted Foxp3 expression in the spleens and mesenteric lymph nodes of DSS-induced colitis mice and in the spleens of the Foxp3GFP mice. Aloperine inhibited Jurkat and mouse naïve T-cell apoptosis. Furthermore, aloperine inhibited PI3K/Akt/mTOR signaling and upregulated PP2A expression in the DSS-induced colitis mice and in Jurkat cells, but LB-100 (PP2A inhibitor) resulted in an elevated Akt activity in Jurkat cells, activated T-cells, and human splenic mononuclear cells. Aloperine inhibited T-cell and lymphocyte proliferation, but LB-100 reverse these effects. In conclusion, aloperine regulates inflammatory responses in colitis by inhibiting the PI3K/Akt/mTOR signaling in a PP2A-dependent manner.

Profiling dendritic cell subsets in the patients with active pulmonary tuberculosis.

Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs). The decreased number of DCs, especially of pDC, seems to be a useful diagnostic marker of APT. Meanwhile, the number of DCs was associated with the prolonged/complicated TB, ATD treatment effect and lymphocyte immune reactions, as manifested that relapsed APT patients with a higher number of tDC and lower number of pDC compared to newly diagnosed patients. Interestingly, mDC from APT patients displayed high expressions of CD83 and CCR7, but pDC displayed low expressions of CD83 and CCR7. Moreover, DCs from APT patients expressed lower levels of HLA-DR and CD80, but expressed a higher level of CD86 than those from HCs. However, the antigen uptake capacity of DC subsets was not different between APT and HCs, despite the antigen uptake capacity of pDC was much lower than that of mDC in both APT patients and HCs. Our data represent a systematic profile of DC subsets in the blood of APT patients, and would represent a useful biomarker for APT.

Role of Interleukin-6 and Its Receptor in Endometriosis.

BACKGROUND Studies have shown that the concentration of interleukin (IL)-6 in peritoneal fluid is increased in patients with endometriosis; however, whether the disorders involving IL-6 contribute to the development of endometriosis is still unclear. In the present study, we evaluated the potential role of IL-6 and IL-6 receptor (IL-6R) in the pathogenesis of endometriosis. MATERIAL AND METHODS We examined activated macrophages and the expression of membrane-binding receptor (mIL-6R) in peritoneal fluid using flow cytometry. The levels of IL-6 and the IL-6 soluble receptor (sIL-6R) in peritoneal fluid and plasma in patients with endometriosis was measured by an enzyme-linked immunosorbent assay. RESULTS Activated macrophages and mIL-6R in peritoneal fluid were increased in patients with endometriosis. IL-6 and sIL-6R in peritoneal fluid were also increased in patients with endometriosis; however, there was an increase in plasma IL-6 and a decrease in plasma sIL-6R. The endometriosis group was categorized into 2 groups according to the retrospective American Fertility Society Score (r-AFS): group A and group B. Peritoneal fluid sIL-6R in endometriosis group B was significantly higher than in endometriosis group A and the control group. CONCLUSIONS Disorders involving IL-6 and IL-6R are correlated with the etiology of endometriosis. An increase in sIL-6R in peritoneal fluid promotes the development of endometriosis by enhancing the bioactivity of IL-6.

A colorimetric indicator-displacement assay for cysteine sensing based on a molecule-exchange mechanism.

In this study, we developed an ingenious yet effective strategy for cysteine detection. The colorimetric cysteine assay is established through an indicator displacement process, where Cu2+ and pyrocatechol violet (PV) was employed as receptor and indicator, respectively. Proof-of-concept trials demonstrated that the stronger binding affinity of Cu2+ receptor toward cysteine than PV indicator endowed our colorimetric sensor with high selectivity and excellent sensitivity as well as with a lower detection limit (4.60µM and 120µM, S/N =3) by UV-visible spectroscopy and the naked eye as the signal readout, respectively. More importantly, the proposed molecule-exchange process in the indicator displacement process could be successfully used to the fabrication of a colorimetric INHIBIT logic gate and even converted into a facile naked eye analysis through paper-based analytical devices for conveniently and reliably detecting cysteine (CySH) in practical applications.

Development and characterization of monoclonal antibody against human IL-37b.

IL-37 has been described as a natural inhibitor of immune responses. Monoclonal antibody (mAb) against human IL-37b with high affinity and specificity can serve as a molecular probe to detect IL-37 and study IL-37 functions, mechanisms and related signal pathways in inflammatory diseases. However, there are very few such mAbs against human IL-37 commercially available so far. In the current study, monoclonal antibodies against human IL-37b were developed by fusing splenocytes from immunized mouse with SP2/0 myeloma cells and polyethylene glycol. Then the antibodies were screened with prokaryotic expressed human IL-37b protein and eukaryotic expressed human IL-37b protein subsequently. Western blot and flow cytometry analysis revealed that selected mAb clons were able to recognize human IL-37 with high specificity. And more importantly, the IL-37b mAbs were fluorescently labeled and can be directly used in flow cytometry and immunohistochemistry. In conclusion, the current study developed new mAbs against human IL-37b, which are applicable in flow cytometry and immunohistochemistry.

BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37.

Roles of human IL-37 in infections remain poorly characterized. Although plasma IL-37 is elevated in patients with tuberculosis (TB), IL-37 source and immune correlate in TB have not been investigated. It is also unknown whether and how TB can influence the ability of immune cells to mount innate responses of IL-37 and pre-inflammatory cytokines. Here, we demonstrated that IL-37b-producing monocytes coincided with a source of elevated plasma IL-37b in TB patients. While IL-37b production in TB was associated with prolonged/complicated TB, TB burdens and inflammatory reactions, it negatively correlated with immune responses of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α or IL-10. Interestingly, mycobacterial re-infection of monocytes from TB patients, but not healthy BCG-vaccinated controls, enhanced or sustained IL-37b production by cultured monocytes. TB-sensitized monocytes from TB patients mounted more robust immune responses of IL-37b than those of pre-inflammatory cytokines during mycobacterial re-infection in culture. Our data represent new findings in terms of IL-37b responses, immune correlates and potential mechanisms in TB patients.

Icariin Inhibits Pulmonary Hypertension Induced by Monocrotaline through Enhancement of NO/cGMP Signaling Pathway in Rats.

It has been reported that icariin (ICA) increased contents of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by improving expression of endothelial nitric oxide synthase (eNOS) and inhibition of phosphodiesterase type 5 (PDE5). In addition, dysfunction of the NO/cGMP pathway may play a crucial role in the pathogenesis of pulmonary hypertension (PH). In this study, the potential protective effects of ICA on PH induced by monocrotaline (MCT, 50 mg/kg) singly subcutaneous injection were investigated and the possible mechanisms involved in NO/cGMP pathway were explored in male Sprague Dawley rats. The results showed that ICA (20, 40, and 80 mg/kg/d) treatment by intragastric administration could significantly ameliorate PH and upregulate the expression of eNOS gene and downregulate the expression of PDE5 gene in MCT-treated rats. Both ICA (40 mg/kg/d) and L-arginine (200 mg/kg/d), a precursor of NO as positive control, notably increased the contents of NO and cGMP in lung tissue homogenate, which were inversed by treatment with (N) G-nitro-L-arginine-methyl ester (L-NAME), a NOS inhibitor, and L-NAME-treatment could also inhibit the protective effects of ICA (40 mg/kg/d) on mean pulmonary artery pressure and artery remodeling and tends to inhibit right ventricle hypertrophy index. In summary, ICA is effective in protecting against MCT-induced PH in rats through enhancement of NO/cGMP signaling pathway in rats.