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OBJECTIVE: To explore the mechanisms of Yangqing Chenfei formula (, YCF) in the treatment of silicosis through a comprehensive strategy consisting of serum pharmacochemistry, network pharmacology analysis, and in vitro validation. METHODS: An ultrahigh-performance liquid chroma-tography-tandem mass spectrometry method was used to confirm the active components in YCF-medicated serum. Then, we obtained targets for active components and genes for silicosis from multiple databases. Furthermore, a protein-protein interaction network was constructed, and Kyoto Encyclopedia of Genes and Genomes pathway and biological process analyses were conducted to elucidate the mechanisms of YCF for the treatment of silicosis. Finally, we validated the important components and mechanisms in vitro. RESULTS: Altogether, 19 active components were identified from rat serum after YCF administration. We identified 724 targets for 19 components, which were mainly related to inflammation [phosphatidy linositol 3 kinase/protein kinase B, forkhead box O, hypoxia inducible factor, and T-cell receptor signaling pathway, nitric oxide biosynthetic process], fibrotic processes [vascular endothelial growth factor signaling pathway, extracellular signal regulated kinase (ERK) 1 and ERK2 cascade, smooth muscle cell proliferation], and apoptosis (negative regulation of apoptotic process). In addition, 218 genes for silicosis were identified and were mainly associated with the inflammatory response and immune process [cytokine?cytokine receptor interaction, tumor necrosis factor alpha (TNF-α), toll-like receptor, and nucleotide binding oligomerization domain-like receptor signaling pathway]. Taking an intersection of active component targets and silicosis genes, we obtained 61 common genes that were mainly related to the inflammatory response and apoptosis, such as the phosphatidylinositol-3-kinase/protein kinase B signaling pathway, mitogen activated protein kinases signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, biosynthesis of nitric oxide, and apoptotic process. In the herb-component-gene-pathway network, paeoniflorin, rutin and nobiletin targeted the most genes. In vitro, paeoniflorin, rutin and nobiletin decreased the mRNA levels of inflammatory factors [interleukin (IL)-6, TNF-α, and IL-1ß], suppressed p-AKT and cleaved caspase-3, and increased B cell lymphoma (Bcl)-2 protein expression in silica-induced macrophages in a concentration-dependent manner. CONCLUSION: YCF could significantly relieve the inflammatory response of silicosis via suppression of the AKT/Bcl-2/Caspase-3 pathway.
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Medicamentos Herbarios Chinos , Farmacología en Red , Silicosis , Silicosis/tratamiento farmacológico , Silicosis/metabolismo , Silicosis/genética , Medicamentos Herbarios Chinos/farmacología , Animales , Ratas , Masculino , Humanos , Transducción de Señal/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , Ratas Sprague-Dawley , Apoptosis/efectos de los fármacosRESUMEN
Objective: To investigate and analyze the influencing factors of simple early breast development in girls, to discover the dangers and triggers of PT conversion to ICPP, and the time point of transformation in order to detect and prevent the occurrence of transformation in advance and reduce the incidence of idiopathic central precocious puberty. Ensure children's physical and mental health and normal growth and development. Methods: A total of 50 children with PT admitted to our hospital from April 2019 to December 2020 were included in the study group, and 50 children with physical examination during the same period were selected as the control group. All children were tested for vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., and IGFBp-3 at 3, 6, 9 and 12 months after the diagnosis of PT. Results: Vitamin D levels decreased in the child, indicating that vitamin D deficiency was closely related to the age of breast development in ICPP girls and may be related to serum P-FSH, P-LH and E2 levels. Increased levels of IGFBp-3 indicate that these indicators are involved in the onset of ICPP. Children have a higher BMI, watch idol dramas or play mobile games longer, often eat snacks containing preservatives, have a fishy diet, are more irritable and sensitive, and dry stools are also risk factors affecting the early development of simple breasts in girls. Conclusion: The influencing factors leading to simple, early breast development in girls include vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., IGFBp-3, and should be combined with the progression of breast Tanner staging (complete regression, recurrent, and persistent), height growth rate, bone age, Uterine and ovarian B ultrasound, sex hormones, etc., warn of the conversion of PT to ICPP, and ensure children's physical and mental health and normal growth and development.
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Background: Traditional Chinese medicine (TCM) is effective for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no objective index for the evaluation of TCM syndrome efficacy. This study aimed to screen biomarkers related to the efficacy of TCM syndrome using metabolomics. Methods: We recruited AECOPD patients with phlegm-heat congesting lung (PH)/phlegm-damp amassing lung (PD) syndrome and treated them with Chinese herbal medicine (Qingre Huatan or Zaoshi Huatan granules) in addition to conventional medicine for 7 days. Data on clinical symptoms and sign scores, modified British Medical Research Council (mMRC), COPD assessment test (CAT), and inflammation indicators, including white blood cell (WBC) count, percentage of neutrophil count (NEU%), and C-reactive protein (CRP), were collected before and after treatment to evaluate the therapeutic effect. Serum samples were collected before and after treatment for metabolomic analysis to screen differential metabolites. Results: A total of 69 patients with AECOPD were enrolled, including 41 and 28 patients in the PH and PD groups, respectively. The clinical symptoms and sign scores, CAT, mMRC, NEU%, and CRP levels after treatment were lower than those before treatment in both groups (p < 0.05). Serum metabolomics analysis showed that there were 13 differential metabolites in the PH group and 16 differential metabolites in the PD group before and after treatment (p < 0.05, variable importance projection (VIP) ≥ 1.00). In the PH group, lysophosphatidylcholine (LPC) (16:0), LPC (17:1), LPC (18:3), LPC (18:2), and LPC (17:0) negatively correlated with clinical symptoms and sign scores (p < 0.05); LPC (16:0), LPC (17:1), LPC (16:1), and LPC (17:0) negatively correlated with WBC (p < 0.05) and NEU% (p < 0.05); and LPC (16:0) negatively correlated with CRP levels. In the PD group, L-phenylalanine positively correlated with CRP levels (p < 0.05), and 2-methylbutyroylcarnitine positively correlated with clinical symptoms and sign (p < 0.05) and CAT scores (p < 0.05). DL-carnitine positively correlated with clinical symptoms and sign scores (p < 0.05). Conclusion: Serum metabolites may be potential indicators to objectively evaluate the efficacy of TCM syndromes; however, further large controlled trials are required to verify these findings.
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OBJECTIVE: To explore the underlying mechanisms of the effects of Yangqing Chenfei formula (, YCF) on inflammation and fibrosis in silicosis via inhibition of macrophage polarization. METHODS: A silicotic rat model was established via a single intratracheal instillation of silica particles on the first day of week 0. Subsequently, YCF was administered intragastrically to silicotic rats during weeks 0-2 and 5-8 twice daily. The mouse-derived alveolar macrophage cell line was used to investigate the mechanisms of YCF in M1/M2 polarization. RESULTS: YCF treatment effectively inhibited lung pathological changes, including inflammatory cell infiltration and tissue damage, and increased the forced expiratory volume in the first 0.3 s, functional residual capacity, and maximal mid-expiratory flow in weeks 2 and 8. Furthermore, the treatment improved lung functions by upregulating tidal volume, pause increase, and expiratory flow at 50% tidal volume from weeks 5 to 8. Moreover, YCF could significantly suppressed the progression of inflammation and fibrosis, by reducing the levels of inflammatory cytokines, as well as collagen- I and III. YCF treatment also decreased the numbers of macrophages and M1/M2 macrophages and the level of transforming growth factor-ß (TGF-ß). Additionally, YCF5, the effective substance in YCF, decreased lipopolysaccharide and interferon-γ-induced M1 macrophage polarization in a concentration-dependent manner. The mechanism of anti-M1 polarization might be related to a decrease in extracellular signal-regulated kinase, c-JUN N-terminal kinase, P38, and P65 phosphorylation. Furthermore, YCF5 inhibited interleukin-4-induced M2 macrophages by decreasing the protein and mRNA expressions of arginase-1 and CD206 as well as the levels of profibrotic factors, such as TGF-ß and connective tissue growth factor. The mechanisms underlying the anti-M2 polarization of YCF5 were primarily associated with the inhibition of the nuclear translocation of phosphorylated signal transducer and activator of transcription 6 (p-STAT6). CONCLUSION: YCF significantly inhibits inflammation and fibrosis in silicotic rats probably via the suppression of M1/M2 macrophage polarization mediated by the inhibition of mitogen-activated protein kinase and nuclear factor kappa B signaling pathways and Janus kinase/STAT6 pathways.
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Neumonía , Dióxido de Silicio , Ratas , Ratones , Animales , Dióxido de Silicio/metabolismo , Dióxido de Silicio/farmacología , Fibrosis , Inflamación/tratamiento farmacológico , Macrófagos , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P<0.05 or P<0.01),significantly increased mean alveolar number and PEF(P<0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P<0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P<0.05 or P<0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P<0.05 or P<0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.
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Objective:To investigate the significance and importance of the interaction between surgeons and engineers during the preoperative planning phase of total knee arthroplasty (TKA) when utilizing patient-specific instrumentation (PSI).Methods:A retrospective review was conducted on 202 knees of PSI-assisted TKA performed on 178 patients between June 2018 and August 2022. The patients' mean age was 68.4±6.2 years, ranging from 53 to 86 years. Among the participants, there were 149 females and 29 males, 93 left knees and 109 right knees. The study involved 171 patients of osteoarthritis (193 knees) and 7 patients of rheumatoid arthritis (9 knees), with 194 knees presenting varus knees and 8 knees with valgus knees. The preoperative plan documents, from the initial engineer-designed plan to the final plan approved by the surgeon, were analyzed to assess the frequency, parameters, and reasons for adjustments made during the planning process.Results:The planning of the 202 PSI-assisted TKA was subjected to at least one round of surgeon-engineer interaction. Among the 202 TKA planning, 117 knees (57.9%) underwent modifications after discussion, with most plans (100 knees, 49.5%) being confirmed after one round of modification. Two rounds of modifications were performed on 10 knees (5.0%), and three rounds on 5 knees (2.5%). A maximum of four rounds of modifications were made on two knees (0.9%). Furthermore, in the case of the remaining 85 knees (42.1%), the surgeons promptly consented to the engineers' initial planning following the discussions. Specific adjustments were made in 106 knees (52.5%) regarding femoral parameters, 57 knees (28.2%) concerning tibial parameters, and 46 knees (22.8%) requiring adjustments to both femoral and tibial parameters. Notably, the most frequently adjusted parameter was the osteotomy thickness of the posterior femoral condyles, which was modified in 94 knees (80.3%). The reasons for adjusting femoral or tibial parameters were summarized, revealing the main factors as follows: 1) Discrepancy between the mediolateral and anteroposterior diameters of the femoral condyle; 2) Twisted deformity of the proximal tibia; 3) Severe flexion contracture deformity of the knee; 4) Collapse of the medial or lateral tibial plateau; 5) Evident anterior arch deformity of the femur.Conclusion:The interaction between surgeons and engineers plays a pivotal role in the preoperative phase of PSI-assisted TKA. Effective collaboration allows surgeons to accurately analyze the unique anatomical characteristics and pathological changes of each patient in a three-dimensional perspective, facilitating the formulation of individualized surgical plans.
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From January 2018 to August 2019, 87 children aged 2 to 8 years with upper gastrointestinal ulcer bleeding were admitted to the Department of Pediatrics of Shangqiu First People′s Hospital. Patients were randomly assigned in two groups, 45 cases received omeprazole for treatment (group A) and 42 cases received ulinastatin and omeprazole for treatment (group B). The omeprazole 10 mg/d was administrated orally for 2 to 4 weeks in two groups, while in group B additional ulinastatin injection (10 000-50 000 IU·kg -1·d -1 was given for 1 week. The effective rate in group B was 95.2% (40/42), which was significantly higher than that in group A (80.0%, 36/45) (χ2=4.567, P=0.03). After treatment, gastroscopy showed that the time of hemostasis, the time of stopping hematemesis, the time of fecal occult blood turning negative, and the length of hospital stay in group B were significantly shorter than those in group A ( P<0.05). The results of flow cytometry showed that the percentages of CD3 + and CD4 + increased and the percentages of CD8 + decreased significantly after treatment in the two groups, while the changes in group B were more marked than those in group A ( P<0.05). Serum inflammatory factors (serum procalcitonin, high-sensitivity C-reactive protein and tumor necrosis α) were significantly reduced after treatment in the two groups, while the above indicators in group A were significantly lower than those in group A (all P<0.05). In group A, there was 1 case of nausea and vomiting, 1 case of abdominal pain and diarrhea, and 1 case of lethargy; in group B, there was 1 case of nausea and vomiting and 1 case of abdominal pain and diarrhea. The study suggests that ulinastatin combined with omeprazole has a better effect than omeprasole alone in treatment of children with upper gastrointestinal ulcer bleeding without increasing adverse effects.
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In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed. Methodologies included HPLC-PDA, HPLC-VWD and UHPLC-MS , combined with principal component analysis (PCA) and partial least squares regression techniques (PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated . PLSR analysis revealed significant positive correlations ( = 0.5795) between the contents of triterpenes , , , and and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.
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Objective To investigate the relationship among the activity of diseases , the alteration of intestinal flora and the serum immuoglobulin (Ig) in patients with ulcerative colitis (UC) and to further evaluate the clinical value of fecal cue ratio in assessing humoral immune abnormalities. Methods Clinical data of 401 UC patients admitted in Peking University First Hospital from January 2013 to May 2015 were analyzed. According to Mayo index , patients were divided into inactive and active groups , and the active group was further divided into the mild, moderate and severe group. Serum immunoglobulin (IgG, IgM, IgA, C3 and C4) and fresh fecal bacteria cue proportion were measured. Statistical analysis was made to find the relevance among the above indexes. Results With the increase of disease activity , the intestinal flora imbalance aggravated (Spearmann correlation coefficient equals 0.295, P < 0.05) and serum IgM decreased significantly. However, serum C3 increased obviously. Serum C4 increased in mild to moderate group but decreased significantly in severe group. With the aggravation of intestinal flora imbalance , serum IgM and IgA decreased but C3 increased (P < 0.05). Conclusions The measurement of intestinal flora cue proportion, Ig, C3 and C4 may contribute to better determining the severity of diseases and provide beneficial information for therapy.
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Objective To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors.Methods Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study.Skin disorders were confirmed by the dermatologists.Clinical data were collected and compared between patients with and without cutaneous manifestations.Results Among the total 373 UC patients,there were 34 cases (9.1%) with cutaneous manifestations,including 11 pyoderma gangrenosum,8 erythema nodosum,6 eczema,3 psoriasis,2 pemphigus,1 granulomatous cheilitis,1 ichthyosis,1 acne rosacea,and 1 impetigo.The skin manifestations may occur after the diagnosis,simultaneously or even before the diagnosis of UC,which were 24,7 and 3 patients respectively.The mean age in patients with skin lesions was (47.2 ± 12.1) years,male to female ratio 0.79∶ 1.More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0% (17/34) vs 25.1% (85/339),P =0.01].In addition,the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5% (26/34) vs 54.6% (185/339),P =0.04].Conclusions The cutaneous manifestations associated with UC are polymorphic,erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients.Skin lesions occur concurrently,pre or post the diagnosis of UC.Skin lesions in UC patients suggest more severe disease activity.Clinicians need to pay more attention to this group.
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Objective To investigate proliferation and apoptosis of colonic epithelial cells from ulcerative colitis (UC)patients with active new-onset,remission and active recurrent stages,and to study the effects of 5-aminosalicylic acid (5-ASA)on proliferation and apoptosis of colonic epithelial cells during the treatment of inducing remission and maintanence remission. Methods From January 2002 to December 2012,twelve patients with mild-to-moderate UC who received treatment and long-term follow-up and achieved remission with 5-ASA and received long-term maintanence treatment with it were assigned to UC group.At the same period,10 healthy individuals with negative endoscopy results or solitary colonic polyp were assigned to control group.The biopsy tissues from colonoscopy for pathological examination of patients in UC group at new-onset active stage,remission stage and recurrence stage were obtained.Levels of proliferation marker Ki-67 and apoptosis of colonic epithelial cells were determined by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)assay,respectively.Data were expressed by median(lower quartile,upper quartile).Kruskal-Wallis test and Mann-Whitney test were performed to compare the differences between groups and Bonferroni method was used for correction.Results The median proliferation indexes (PI)of colonic epithelial cells of UC patients at new-onset active period,remission period and recurrent active period were 31 .65 % (19.14%,39.66%), 12.30% (11 .11 %,14.10%) and 44.15 % (33.65 %,52.45 %), respectively,which were all higher than those of control group (7.89% (6.54%,8.86%))there were statistically significant differentes among four groups (H =30.033,P <0.01 );those of new onset active period and recurrent active period were both higher than remission period,and the differences were statistically significant (all P <0.05/6).The median apoptosis indexes (AI)of colonic epithelial cells in UC patients at new-onset active period,remission period and recurrent active period were 24.18%(17.81 %,27.16%),44.19% (43.41 %,50.55 %),41 .24% (33.78%,46.24%),respectively,which were all higher than those of control group (2.65 %(2.48%,2.98%)),there were statistically significant differences among four groups (H =31 .563,P <0.01);and those of remission and recurrent active period were both higher than new-onset active period (all P <0.05/6).The median apoptosis/proliferation ratios of control group,new onset active period,remission period and recurrent active period were 0.320 0 (0.275 5 ,0.425 0),0.749 9 (0.634 9,1 .115 8 ),3.282 8 (3.133 1 ,4.406 8 )and 1 .008 2 (0.801 9, 1 .099 2),respectively,there were statically significant differences among four groups (H =29.441 ,P <0.01);those of new onset active period and recurrent active period were both lower than that of remission period and the differnces were statistically significant (both P <0.05/6 ).Conclusions Proliferation and apoptosis imbalance in colonic epithelial cells of UC patients is one of the important mechanisms for the pathgensis of UC.5-ASA does not promote the proliferation of epithelial cells during UC remission period.
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Objective To discuss the clinical value of transesophageal echocardiography used in extracorporeal circulationcardiac valve replacement. Methods 89 patients received extracorporeal circulation cardiac valve replacement in our hospital from January 2012 to December 2014 were included in the study. Transesophageal echocardiography were performed preoperatively, intraoperation and postoperatively and the findings were compared to the result of preoperation transthoracic echocardiography exam. The measurement of aortic annulus diameter and detection rates of calcification obtained by transthoracic and transesophaged echocardiography were compared. Changes in heart function parameters before and after operation were compared. The alternations in surgery plan made after pre-operative transesophageal echocardiography exam and any relevant treatment or procedure performed according to intra-operation transesophageal echo findings were recorded. All the patients were followed up for 6 months - 40 months. Results Before extracorporeal circulation cardiac valve replacement, the aortic annulus diameter measured and detection rates of calcification by transthoracic echocardiography were smaller and lower than actual surgical pathology results ( P 0. 05 ) . Conclusions For patients receiving extracorporeal circulation cardiac valve replacement, transesophagus echocardiography examination is helpful to guide the selection of valve stent and operation methods.
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Objective To investigate the clinical characteristics of elderly-onset inflammatory bowel disease (IBD) and its treatment options.Methods Clinical data of IBD in-patients treated in Peking University First Hospital from January 1995 to December 2014 were reviewed and the subsequent information in the follow-up was also collected.Based on the onset age, patients were divided into the elderly-onset group (≥60 years old) and the control group (<60 years old).The general situation, clinical characteristics and treatment options were retrospectively analyzed and compared between the two groups.Results There were 37 patients (9.3%) with IBD in the elderly-onset group, with 25 cases with ulcerative colitis (UC) and 12 cases with Crohn disease (CD).The ratio of gender, smoking, family history of IBD and colon cancer in the elderly-onset and control groups were 1 : 0.9 and 1 : 1.3, 32.4% and 21.7%, 0.0% and 6.1%, 0.0% and 1.9%, respectively, with no significant differences between the two group (P=0.597, 0.139, 0.247 and 0.840).The attack frequency and the percentages of patients with persistent symptoms and severe disease had no statistical differences between the elderly onset and the control groups.Compared with the control group, the elderly-onset group showed that the percentage of UC patients with extensive colitis (E3) was decreased [16.0% (4/25) vs.41.2% (117/289) respectively (x2 =6.123, P=0.013)], and the percentage of CD patients with colonic type (L2) was increased [58.3% (7/12)vs.21.3% (16/75) respectively (x2=6.447, P=0.011)].For treatment options, the number of patients receiving 5-Aminosalicylic Acid (5-ASA)/sulfasalazine(SASP) as maintenance treatment for more than 1 years were 274 cases (96.9%) in the control group and 22 cases (86.5%) in the elderlyonset group (x2 =6.382, P=0.011).And the number of patients receiving systemic corticosteroids during induction period were 5 cases (19.4%) in the elderly-onset group and 122 case (43.2%) in the control group (x2 =7.617, P=0.006).There were no statistically significances in the number of patients with immunosuppressant, biologics and operation treatment between the two groups.Conclusions The elderly-onset IBD patients are not rare.The inflammation involvement is more limited in the elderly-onset patients than in the young-onset patients.The treatment option for elderlyonset IBD should be more cautious, especially for the treatment with 5-ASA/SASP long-term maintenance and systemic corticosteroids usage.
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Mammalian target of rapamycin( mTOR) is a key reg-ulator of aging and aging-related diseases. Rapamycin ( RAPA) induces and promotes the process of cell autophagy through in-hibiting mTOR pathway. Autophagy exerts a crucial role in main-taining the cellular meostasis, which provides essential materials for cell reconstruction, regeneration and repair via degradating the redundant, damaged, or senescent proteins and organelles. Hutchinson Gilford progeria syndrome ( HGPS ) patients are al-ways accompanied with abnormally accumulated progerin in cells. Similar to HGPS, abnormal protein accumulation is the common pathological feature of neurodegenerative diseases, in-cluding Huntington′s disease, Parkinson′s disease, Alzheimer′s disease and so on. Degradation of these abnormal proteins pre-dominantly depends on cell autophagy. Thus, rapamycin is a po-tential anti-aging drug for HGPS and aging-related diseases thera-py. This view focuses on the effects of rapamycin on cell autoph-agy and clinical application in HGPS and neurodegenerative dis-eases.
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<p><b>OBJECTIVE</b>To investigate the correlation between miR-124 rs531564 polymorphisms and the susceptibility to cervical cancer in Chinese Han women in Guangdong Province.</p><p><b>METHODS</b>The genotypes of miR-124 rs531564 polymorphism were determined using polymerase chain reaction-based ligase detection reaction (PCR-LDR) in 107 cervical cancer patients and 208 healthy female blood donors. The correlation between the polymorphism and the susceptibility to cervical cancer was evaluated using unconditional logistic regression analysis.</p><p><b>RESULTS</b>The incidence of HPV infection in the patients (93.1%) was much higher than that in the control subjects (16.8%, P<0.001), suggesting the importance of HPV infection as a critical risk factor for cervical cancer. The G allele of miR-124 rs531564 polymorphism in the cervical cancer patients was much less frequent than that in the controls (8.0% vs 15.1%, P=0.014), suggesting its possible role as a protective allele. Compared with those carrying CC genotype, individuals carrying the CG and GG genotypes showed a significantly reduced risk for cervical cancer (OR=0.47, 95% CI=0.26-0.88, P=0.017), and this protective role of the G allele was more prominent in older women (≥45 years old) (OR=0.28, 95% CI=0.10-0.76, P=0.012).</p><p><b>CONCLUSION</b>miR-124 rs531564 polymorphism may play a role in cervical cancer susceptibility in Chinese Han women, and G allele is associated with a reduced risk of cervical cancer.</p>
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Adulto , Femenino , Humanos , Persona de Mediana Edad , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , MicroARNs , Genética , Polimorfismo de Nucleótido Simple , Neoplasias del Cuello Uterino , GenéticaRESUMEN
Objective To investigate the change of the distribution of peripheral blood lymphocyte subsets,before and after treated by infliximab (IFX) in patients with inflammatory bowel disease (IBD).Methods From September 2008 to January 2013,a total of 20 patients with IBD accepted more than three times of IFX treatment and on time follow-up were collected,11 cases of ulcerative colitis (UC) and nine of Crohn's disease (CD).At same time,20 healthy individuals were enrolled as healthy control group.The efficacy of IFX on patients with UC or CD was evaluated according to Mayo score and simplified Crohn's disease active index (CDAI) before and after treatment.Fasting blood of healthy control group,one day before IFX treatment and in 24 to 72 hours after the third time of IFX injection of IBD patients was collected.The percentage of total T lymphocyte,total B lymphocyte,CD4+ T lymphocyte,CD8+ T lymphocyte and natural killer (NK) cell in lymphocyte was determined by fluorescent labeled monoclonal antibodies and flow cytometry.Independent sample t-test was performed for comparison between two groups.Analysis of variance was for comparison among three groups.Results Three of 11 patients with UC achieved clinical remission,three cases were clinical improved and five cases were ineffectiveness.Among nine CD patients,one achieved clinical remission,six cases were clinical improved and two cases were ineffectiveness.Of UC patients,the percentage of total T lymphocyte before and after treatment ((84.2±8.1) % and (82.1±6.2)%),the percentage of CD8+ T lymphocyte before treatment ((40.0± 13.2)%) were all higher than that of healthy control group ((74.7±10.7)% and (30.5±11.9) %),while the percentage of NK cell before and after treatment ((5.1±2.8)% and (7.8±4.3)%) were all lower than that of healthy control group ((13.7 ±7.8)%) and the differences were statistically significant (t=2.540,2.074,2.251,3.464 and 2.063,all P<0.05).Compared with healthy controls,there were no significant differences in the percentage of total B lymphocyte and CD4+ T lymphocyte of UC patients before and after treatment,the percentage of total T lymphocyte,total B lymphocyte,CD4+ T lymphocyte,CD8+T lymphocyte and NK cell of CD patients before and after treatment (all P>0.05).Before treatment,there were significant differences among effective treatment group,ineffective treatment group and healthy control group in the percentage of total T lymphocyte,CD8+ T lymphocyte and NK cell (F=4.095,4.571 and 7.432,all P<0.05),of those there were significant differences between ineffective treatment group ((88.3 ± 8.2) %,(44.4 ± 11.5) % and (4.6 ± 3.2) %) and healthy control group (t=2.902,2.105 and 3.647,all P<0.05).Conclusion The percentage of peripheral blood total T lymphocyte and CD8+T lymphocyte increase in active IBD patients with ineffective IFX treatment,however the percentage of NK cell decreases.
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Objective To study the role of saccharomyces cerevisiae DRE2 in endoplasmic reticulum response induced by tunica‐mycin .Methods The der2 ::URA3 gene deletion cassette was amplified from the wild type genomic DNA by PCR ;DRE2 deficiency heterozygote strain was made by gene recombination .The heterozygote strain resistant ability to tunicamycin and the replicative li‐fespan were analyzed in this study .Results DRE2 deficiency strain was resistant to tunicamycin ,but the replicative lifespan was decreased compared to wild type strain (P< 0 .05) .Conclusion DRE2 may be involved in the yeast endoplasmic reticulum response and replicative lifespan regulation .
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Objective To investigate the effects of trimebutine maleate (TM) on the expression of large conductance calcium-activated potassium channel (BKCa) and ryanodine receptors (RyR)channels at mRNA and protein level in colonic smooth muscle cell of cold restraint stress(CRS)induced rats.Methods A total of 24 Wistar rats were divided into CRS group,CRS with TM group and control group equally.The rats of CRS group were gavaged with 0.9%NaCl (6 ml/kg) daily; the rats of CRS with TM group were gavaged with 15 g/L TM (6 ml/kg) daily and activity was restricted in wire cage at 4 ℃ for two hours,continuously for five days.The rats of control group were gavaged with 0.9 % NaCl (6 ml/kg) once without CRS.The amount and characteristics of stool of rats in each group were observed.The colonic smooth muscle was isolated to detect the expression of BKCa and RyR at mRNA and protein level by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results The median of rats defecation particles of CRS group was six,control group was one and CRS with TM group was five.Compared with control group,the defecation appearance of CRS group and CRS with TM group was looser and wetter observed by naked eyes.Compared with control group,there was no obvious pathological changes in CRS and CRS with TM group.There was no significant difference in the mRNA expression of BKCa and RyR channels between control group and CRS group.Compared with control group,the BKCa expression at mRNA level of CRS with TM group increased 1.45 fold.Compared with control group,the RyR2 expression at mRNA level of CRS with TM group increased 1.32 fold.Compared with control group,the BKCa expression at protein level of CRS with TM group increased 1.39 fold,and there was no RyR2 expression band at protein level.Conclusion TM might affect colonic smooth muscle contraction through the upregulation of BKCa expression at mRNA and protein level and RyR expression at mRNA level.
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Objective To determine the effect of proinflammatory cytokines including interleukin-lbeta (IL-1β) and tumor necrosis factor-Alpha (TNF-α) on human serotonin transporter (SERT) in human enterocyte-like cell line Caco-2.Methods Caco2 cells were cultured for 5 days,then were divided into control group.IL-1β treated group (50 ng/ml) and TNF-α treated group (50ng/ml) for 2.24,48 and 72 hours.The expression of SERT mRNA was detected by RT-PCR at 2,24 and 48 hours and its protein expression was measured by Western blotting at 24,48 and 72 hours.Results The expression of SERT mRNA at 2,24 and 48 hours was lower both in IL-1β treated group (1.393±1.184,1.064±0.625 and 1.013±0.415,respectively) and TNF-α treated group (1.000±0.000,0.829±0.162and 0.945±0.147,respectively) in comparison with control group (2.282±1.367,1.586±0.421 and 1.86 ±O.496,respectively).There was significant difference among three groups (P<0.01).The expression of SERT protein at 24,48 and 72 hours was lower in IL-1β treated group and TNF-α treated group than in control group.Conclusions The IL-1β and TNF-α can inhibit the expressions of SERT mRNA and protein in Caco-2 cells,which indicates that IL-1β and TNF-α may change visceral sensitivity by influencing peripheral 5-hydroxytryptamine levels.
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Objective To assess the expression of TNFα, IL-1β and the serotonin transporter (SERT) in adult rats of chronic visceral hypersensitivity induced by colon irritation during postnatal development, and to provide evidence to clarify the complex relationship between inflammatory cytokines and SERT among visceral hypersensitivity. Methods Sixteen neonatal male Sprague-Dawley rats were randomly separated into two groups undergoing different treatments. The irritated group ( n = 8 ) was received intracolonic injections of acetic acid(0.5%) between postnatal days 8 and 21 and another group ( n = 8 )was received colonic infusion with 0. 9% saline served as control. When they became adults( ages 7 weeks),the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention (RD) to evaluate visceral hypersensitivity. Histological evaluation and MPO activity assay were performed to quantify the inflammation. The expression of cytokine of colon was assessed through immunohistochemistry. The expression of SERT was examined by Western blot. Results Histological examination of the tissues showed no significant structural damage or loss of crypts. The MPO levels in both groups were similar[(0. 497 ±0. 570) unit/g vs (0. 623 ±0. 739) unit/g, P =0.724]. The threshold to elicit a distinctive abdominal muscle contraction in response to RD decreased from (0.40 ±0. 14) ml in the control group to (0. 19 ±0.06)ml in the irritated group. And the threshold for bodying arching decreased from (0.91 ± 0. 26 ) ml in the control group to ( 0. 47 ± 0. 13 ) ml in the irritated group (P < 0. 01 ). Cytokine immunoreactivity was increased in the irritated group when compared to the control group (TNFα: 0. 194 ±0. 001 vs 0. 182 ±0. 001, P <0. 01; IL-1β: 0. 196 ±0. 002 vs 0. 185 ±0.001, P<0. 01 ), while SERT expression were reduced in the irritated group (0. 298 ±0. 038 vs 0. 634 ±0. 200, P<0. 05). Conclusion There is an increase in the proinflammatory cytokines and a decrease in the SERT expression associated with the presence of chronic visceral hypersensitivity, both of them may play an important role in the pathogenesis of visceral hypersensitivity.