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1.
Cardiovasc Diabetol ; 23(1): 86, 2024 02 28.
Article in English | MEDLINE | ID: mdl-38419039

ABSTRACT

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.


Subject(s)
Coronary Disease , Hypertension , Insulin Resistance , Humans , Longitudinal Studies , Nutrition Surveys , Blood Glucose , Cohort Studies , Hypertension/diagnosis , Coronary Disease/diagnosis , Triglycerides , Glucose , Biomarkers
2.
Acta Pharmacol Sin ; 45(3): 609-618, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38030799

ABSTRACT

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.


Subject(s)
Antineoplastic Agents , Immunoconjugates , Single-Domain Antibodies , Humans , Animals , Mice , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Immunoconjugates/pharmacology , Immunoconjugates/therapeutic use , Cell Adhesion Molecules , Cytotoxins , Xenograft Model Antitumor Assays , Carcinoembryonic Antigen , GPI-Linked Proteins
3.
Acta Pharmacol Sin ; 43(4): 954-962, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34234269

ABSTRACT

Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.


Subject(s)
Antibodies, Monoclonal , Bacteriophages , Animals , Cell Surface Display Techniques , Germ Cells , Humans , Mammals , Peptide Library
4.
Ecotoxicol Environ Saf ; 233: 113306, 2022 Mar 15.
Article in English | MEDLINE | ID: mdl-35183812

ABSTRACT

Exposure to cadmium (Cd), a toxic metal, is epidemiologically linked to nonalcoholic steatohepatitis (NASH) in humans. However, the role of Cd in NASH remains to be fully elucidated. This study employed a novel murine NASH model to investigate the effects of chronic low-dose Cd on hepatic pathology and its underlying mechanisms. NASH is characterized by lipid accumulation, extensive cell death, and persistent inflammation in the liver. We found that treatment with Cd in drinking water (10 mg/L) for 6 or 12 weeks significantly boosted hepatic fat deposition, increased hepatocyte destruction, and amplified inflammatory responses in mice, confirming that low-dose Cd can facilitate NASH development in vivo. Mechanistically, chronic Cd exposure reshaped the hepatic transcriptional landscape, with PPAR-mediated fatty acid metabolic pathways being the most significantly altered. In particular, Cd repressed fatty acid desaturation, leading to the accumulation of saturated fatty acids whose lipotoxicity exacerbated cell death and, consequently, inflammatory activation. In summary, we validated the causal effects of chronic low-dose Cd on NASH in vivo and identified the fatty acid desaturation program as a novel target for Cd to instigate hepatopathological alterations.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Cadmium/metabolism , Fatty Acids/metabolism , Hepatocytes/metabolism , Liver , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/chemically induced
5.
Appl Microbiol Biotechnol ; 104(1): 107-117, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31734810

ABSTRACT

Vaccination has been regarded as the most effective way to reduce death and morbidity caused by infectious diseases in the livestock industry. In this study, plasma activated water (PAW) was introduced to prepare the inactivated Newcastle disease vaccine. Humoral immune response was tested by hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). In addition, cell-mediated immune response was evaluated by lymphocyte proliferation assay and flow cytometry. The results demonstrated that the vaccine prepared by PAW at appropriate volume ratio could induce similar antibody titers in specific pathogen-free (SPF) chickens compared with the formaldehyde-inactivated vaccine. The challenge experiment further confirmed that the vaccine prepared by PAW conferred solid protection against virulent NDV. Moreover, it was found that the vaccine could promote the proliferation of lymphocytes and stimulate cell-mediated immunity of SPF chickens. Furthermore, analysis of electron spin resonance (ESR) spectroscopy and physicochemical properties of PAW suggested reactive oxygen and nitrogen species (RONS) played an essential role in the virus inactivation. Therefore, this study indicated that NDV treated by PAW in an appropriate ratio retained immunogenicity on the premise of virus inactivation. PAW as a promising strategy could be used to prepare inactivated vaccine for Newcastle disease.


Subject(s)
Newcastle Disease/prevention & control , Newcastle disease virus/immunology , Plasma Gases/chemistry , Viral Vaccines/immunology , Water/analysis , Animals , Antibodies, Viral/blood , Chickens/immunology , Hemagglutination Inhibition Tests , Immunity, Cellular , Immunity, Humoral , Lymphocyte Activation , Poultry Diseases/prevention & control , Poultry Diseases/virology , Specific Pathogen-Free Organisms , Vaccines, Inactivated , Viral Vaccines/administration & dosage
6.
Appl Opt ; 57(24): 7070-7075, 2018 Aug 20.
Article in English | MEDLINE | ID: mdl-30129601

ABSTRACT

We present the results of numerical simulation of a dissipative solitons mode-locked fiber laser working over 1.6 µm. First, systematic and computationally intensive analysis of high-energy-pulse nonlinear phase shift of a fiber laser was conducted, and we numerically simulated dissipative solitons pulse evolution. In addition, we employed a method named A/B ratio to decrease B-integral by changing the distribution of passive fiber in the ring cavity. This method inhibited the accumulation of nonlinear phase shift and effectively enlarged the pulse energy from 0.8 nJ to 3.6 nJ. Finally, we optimized linear chirp of the pulse by using a designed larger-mode-area fiber, and ultimately a 2.82-kW, 650-fs pulse was obtained.

7.
J Med Virol ; 89(11): 1988-1994, 2017 11.
Article in English | MEDLINE | ID: mdl-28577316

ABSTRACT

Hepatitis E virus (HEV) infection is a serious public health concern in developing countries. China is regarded as an HEV-endemic area, but epidemiological data for HEV among different nationalities is limited. This study was conducted to estimate the seroprevalence and risk factors of HEV infection in Koreans (n = 520), Manchus (n = 303), Mongols (n = 217), and Hans (n = 802) in Eastern and Northeastern China between 2013 and 2015. A total of 366 (19.87%) out of 1842 samples were seropositive for IgG or IgM HEV-antibodies detected by enzyme-linked immunoassays. Among these groups, the Mongols had the highest seroprevalence of HEV infection (25.35%, 55/217), followed by the Koreans (23.65%, 123/520), the Manchus (19.80%, 60/303), and the Hans (15.96%, 128/802). Multiple analysis showed that the gender, consumption of raw/undercooked meat, source of drinking water, residence area, and age were significantly associated with HEV infection in four ethnic groups. The present results indicated that HEV infection was prevalent in Mongols, Koreans, Manchus, and Hans in the surveyed regions, which demonstrated the higher risk of transmitting HEV in multiple nationalities in Eastern and Northeastern China.


Subject(s)
Hepatitis Antibodies/blood , Hepatitis E virus/immunology , Hepatitis E/ethnology , Seroepidemiologic Studies , Adolescent , Adult , Aged , Asian People , Child , Child, Preschool , China/epidemiology , Enzyme-Linked Immunosorbent Assay , Ethnicity , Female , Hepatitis E/immunology , Hepatitis E/virology , Hepatitis E virus/isolation & purification , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , Risk Factors , Young Adult
9.
Parasitol Res ; 114(12): 4725-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26403980

ABSTRACT

Toxoplasma gondii is a zoonotic protozoan of almost all species of mammals and birds. However, no information is available about seroprevalence of the pathogen in stray dogs in seven cities from Inner Mongolia, Jilin, Liaoning province, China. Using the indirect hemagglutination antibody (IHA) test with a cutoff titer of 1:64, 129 (14.05 %) out of 918 stray dogs were surveyed to be T. gondii seropositive. Analysis of the risk factor showed that there was no statistical difference of seroprevalence of T. gondii between males (13.46 %) and females (14.54 %) (P > 0.05). The seropositive rates of T. gondii infection in stray dogs among the seven cities in northern China were significant statistically different (P = 0.005). Moreover, seroprevalence of T. gondii in dogs were varied from 11.01 % (95 % CI 6.94-15.09) to 16.86 % (95 % CI 12.27-21.46) among different age groups, and the difference was statistically significant (P = 0.03). More importantly, T. gondii seropositive in stray dogs has a declining tendence from 2011 to 2015 (P = 0.004). The results of the present study showed that stray dogs in Inner Mongolia, Jilin, Liaoning province, China are exposed to T. gondii, for the first time, and could also provide a foundation data for prevent and control T. gondii infection in dogs, other animals and humans.


Subject(s)
Antibodies, Protozoan/blood , Dog Diseases/parasitology , Toxoplasma/isolation & purification , Toxoplasmosis, Animal/parasitology , Animals , China/epidemiology , Cities , Dog Diseases/blood , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Dogs , Female , Hemagglutination Tests , Humans , Male , Risk Factors , Seroepidemiologic Studies , Toxoplasma/immunology , Toxoplasmosis, Animal/blood , Toxoplasmosis, Animal/diagnosis , Toxoplasmosis, Animal/epidemiology
10.
Front Cardiovasc Med ; 11: 1308592, 2024.
Article in English | MEDLINE | ID: mdl-38327493

ABSTRACT

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

11.
IEEE Trans Vis Comput Graph ; 29(10): 4172-4182, 2023 Oct.
Article in English | MEDLINE | ID: mdl-35709112

ABSTRACT

Automatic generation of fonts can greatly facilitate the font design process, and provide prototypes where designers can draw inspiration from. Existing generation methods are mainly built upon rasterized glyph images to utilize the successful convolutional architecture, but ignore the vector nature of glyph shapes. We present an implicit representation, modeling each glyph as shape primitives enclosed by several quadratic curves. This structured implicit representation is shown to be better suited for glyph modeling, and enables rendering glyph images at arbitrary high resolutions. Our representation gives high-quality glyph reconstruction and interpolation results, and performs well on the challenging one-shot font style transfer task comparing to other alternatives both qualitatively and quantitatively.

12.
Environ Sci Technol ; 46(5): 2911-7, 2012 Mar 06.
Article in English | MEDLINE | ID: mdl-22304368

ABSTRACT

A large amount of organophosphate pesticides (OPs) is used throughout China. Animal studies have suggested that even moderate doses are toxic to neurodevelopment, but there are a few studies in humans. We investigated both the urinary levels of OP metabolites in children and their relationship with child neurodevelopment. Participating 301 young children (23-25 months of age) were recruited from two community hospitals in Shanghai between February and October 2008. We measured five nonspecific dialkyl phosphate (DAP) metabolite levels of OPs in the children's urine and examined their association with the children's developmental quotients (DQs) based on the Gesell Developmental Schedules (GDS). The creatinine-adjusted geometric means (GMs) of OP metabolites in urine samples were 11.27 µg/g for DMP; 6.99 µg/g for DMTP; 7.96 µg/g for DEP; 14.19 µg/g for DETP; and 4.55 µg/g for DEDTP. The children had relatively higher levels of OP urinary metabolites compared with those reported in developed countries, no association was found between child urinary levels of OP metabolites and any of the DQ scores. However, our results should be interpreted with caution, and more studies of children living in China are warranted given the relatively high levels of child OP urinary metabolites in Shanghai.


Subject(s)
Environmental Exposure/analysis , Nervous System/growth & development , Organophosphorus Compounds/urine , Pesticides/urine , Child , Child Development , Child, Preschool , China , Creatinine/metabolism , Demography , Environmental Monitoring , Female , Humans , Language , Male , Motor Activity/physiology
13.
Zhonghua Yi Xue Za Zhi ; 92(48): 3426-8, 2012 Dec 25.
Article in Zh | MEDLINE | ID: mdl-23327705

ABSTRACT

OBJECTIVE: To explore the clinical characteristic and therapeutic strategies of acute appendicitis after radical gastrectomy for gastric carcinoma. METHODS: The clinical data of 31 patients with acute appendicitis after radical gastrectomy for gastric carcinoma from January 2006 to January 2012 was analyzed retrospectively. The profiles of previous operations, symptoms, physical signs, disease duration, progression time, examination results, peri-operative complications, results of bacterial culture and use of antibiotics were used to evaluate the clinical characteristics and therapeutic strategies. RESULTS: There were 19 males and 12 females with a mean age of (61 ± 4) years. Gastric cancer postoperative acute appendicitis lacked typical symptoms. The presenting symptoms were persistent and progressive severe right lower abdominal pains (n = 31, 100.0%), associated, with fever (n = 27, 87.1%) nausea or vomiting (n = 11, 35.5%), abdominal distension (n = 9, 29.0%), intestinal obstruction (n = 21, 67.7%) and abdominal purulent exudate (n = 31, 100.0%). The average onset time from abdominal pain to peritonitis was (15 ± 4) hours. Perforated appendix occurred in 16 cases (51.6%). Seven patients had no increase of the total number of WBC or percentage of neutrophils (22.6%). Exploratory laparotomy was performed in 17 cases, and the rate of delayed diagnosis was 54.8%. And 31 patients were cured by surgery and anti-infection treatment. There was no intraoperative death. CONCLUSIONS: Because of rapidly spreading abdominal infection, peritonitis occurs early with a high incidence rate. Early diagnosis, early operation and rational use of antibiotics are the most important therapeutic modalities of acute postoperative appendicitis in patients with gastric cancer.


Subject(s)
Appendicitis/diagnosis , Appendicitis/etiology , Gastrectomy/adverse effects , Postoperative Complications , Stomach Neoplasms/surgery , Acute Disease , Aged , Appendicitis/drug therapy , Female , Humans , Male , Middle Aged , Retrospective Studies
14.
Nat Prod Res ; : 1-9, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36059228

ABSTRACT

A new alkaloid, demethylorychophragine A (1), together with 18 known compounds was isolated from the aerial parts of Orychophragmus violaceus. Structure of the new compound was identified by extensive spectroscopic techniques. 2 and 3 were isolated from nature for the first time. Known compounds were identified by comparison with data reported in the literature. All compounds were evaluated for anti-radiation activities against X-ray irradiation in HUVEC cell line. Results showed that 10, 12, and 15 showed excellent anti-radiation activity. All compounds were tested for cytotoxic activity against SH-SY5Y and HeLa cell lines. 16 exhibited significant cytotoxicity activity against SH-SY5Y cells, with IC50 value of 23.86 ± 0.38 µM (p = 0.045). The anti-inflammatory effects of all compounds were assessed by determining their ability to inhibit the production of NO, which was induced by stimulating the RAW264.7 murine macrophage cell line with lipopolysaccharide. 16 markedly decreased NO to a level of 27.34 ± 1.29 µM.

15.
IEEE Trans Vis Comput Graph ; 28(12): 3986-3999, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34506285

ABSTRACT

In this article, we propose a system that can automatically generate immersive and interactive virtual reality (VR) scenes by taking real-world geometric constraints into account. Our system can not only help users avoid real-world obstacles in virtual reality experiences, but also provide context-consistent contents to preserve their sense of presence. To do so, our system first identifies the positions and bounding boxes of scene objects as well as a set of interactive planes from 3D scans. Then context-consistent virtual objects that have similar geometric properties to the real ones can be automatically selected and placed into the virtual scene, based on learned object association relations and layout patterns from large amounts of indoor scene configurations. We regard virtual object replacement as a combinatorial optimization problem, considering both geometric and contextual consistency constraints. Quantitative and qualitative results show that our system can generate plausible interactive virtual scenes that highly resemble real environments, and have the ability to keep the sense of presence for users in their VR experiences.

16.
J Tradit Chin Med ; 42(5): 764-772, 2022 10.
Article in English | MEDLINE | ID: mdl-36083484

ABSTRACT

OBJECTIVE: To determine whether Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole (IVSd) and the thickness of the posterior wall at the end of diastole (PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced ( < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased ( < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group ( < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased ( < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group ( < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.


Subject(s)
Heart Failure , Animals , Aorta, Abdominal/metabolism , Constriction , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/genetics , Cyclic GMP-Dependent Protein Kinases/metabolism , Diastole , Guanosine Monophosphate , Heart Failure/drug therapy , Heart Failure/genetics , Male , Rats , Signal Transduction , Stroke Volume/physiology
17.
Pediatr Surg Int ; 27(11): 1203-12, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21691763

ABSTRACT

PURPOSE: Kidney ischemia-reperfusion injury (IRI) after kidney transplant remains a major problem, separate from immune rejection that can lead to kidney transplant failure and graft function loss. Free radicals, disturbance of microcirculation and the inflammatory cascade appear to be the main contributors. Radix Codonopsis, a traditional Chinese drug used in vascular diseases, is an antioxidant and free radical scavenger. This study investigates the protective effect and underlying mechanisms of Radix Codonopsis extract saponins on kidney transplantation. METHODS: Renal transplantation was performed after rat kidneys had been stored for 1 h at 4°C. Blood urea nitrogen (BUN), serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed; bcl-2 and bax mRNA expression was detected using RT-PCR; bcl-2 and bax protein expression was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) was used to detect apoptotic cells and determine the apoptosis index (AI). Analysis of variance (ANOVA) followed by Dunnett's test was used when more than two groups were compared. RESULTS: Saponin-treated animals showed increased SOD levels accompanied by decreased MDA, Scr and BUN levels (p < 0.05 vs. untreated controls); bcl-2 mRNA and protein levels were increased in transplanted kidney from treated animals, while bax mRNA and protein levels were decreased (p < 0.05 vs. untreated controls). AI was significantly decreased in transplanted kidneys from treated animals relative to untreated controls (p < 0.05 vs. untreated controls). CONCLUSION: This study clearly demonstrates the protective effects on IRI after kidney transplantation, which may be explained by decreased lipid peroxidation and inhibition of apoptosis.


Subject(s)
Codonopsis , Graft Rejection/prevention & control , Kidney Transplantation/adverse effects , Oxidative Stress/drug effects , Plant Extracts/therapeutic use , Reperfusion Injury/prevention & control , Animals , Apoptosis/drug effects , Disease Models, Animal , Free Radical Scavengers/metabolism , Graft Rejection/metabolism , Graft Rejection/pathology , Immunohistochemistry , In Situ Nick-End Labeling , Male , Malondialdehyde/metabolism , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reverse Transcriptase Polymerase Chain Reaction , Superoxide Dismutase/metabolism , Treatment Outcome , bcl-2-Associated X Protein/biosynthesis , bcl-2-Associated X Protein/genetics
18.
Zhonghua Yi Xue Za Zhi ; 91(4): 247-50, 2011 Jan 25.
Article in Zh | MEDLINE | ID: mdl-21418869

ABSTRACT

OBJECTIVE: To evaluate the relationship among the microalbuminuria, surgical stress and postoperative fluid balance after abdominal surgery. METHODS: A total of 191 patients undergoing an elective abdominal operation were studied. According to the extent of operative trauma, all patients were divided into 4 groups. GroupI: laparoscopic cholecystectomy (n=64); Group II: laparotomy of cholecyst and biliary tract (n=36); Group III: radical surgery of colorectal cancer (n=43); Group IV: distal subtotal gastrectomy (D2) or total gastectomy (D3) or pancreaticoduodenectomy (n=48). The operative severities were predicated by surgical stress score (SSS). Urine albumin-creatinine ratio (ACR) was measured at both pre- and post-operation. The levels of ACR were compared by ANOVA among these 4 groups. The correlation of ACR and SSS was analyzed. In Groups III and IV, body weight was measured by weight-bed simultaneously. The correlation of variation of ACR at 0 and 6 hours post-operation (ΔACR) and the volume of positive fluid balance in the first 24 hour post-operation were studied. We also compared the varied durations of ACR levels returning to normal or the pre-operative level and body weight reaching peak values. RESULTS: The levels of ACR increased in all groups. The level of ACR was the highest in Group IV and the lowest in Group I, significantly different from the levels of group II and III. There was a significant positive correlation between the increase in ACR and the severity of surgical trauma as measured by SSS. A positive correlation was observed between the volume of positive fluid balance in the first 24 hour post-operation and ΔACR at 0 and 6 hours post-operation. The varied duration of ACR levels returning normal or the pre-operative level was earlier than that of reaching the peak values. CONCLUSION: ACR has a positive correlation with the extent of surgical stress and volume of positive fluid balance. The fact that the ACR comes earlier than the change of body weight indicates that the change of ACR is a more sensitive and simpler parameter than body weight to predict the onset of negative fluid balance.


Subject(s)
Abdomen/surgery , Albuminuria/metabolism , Albuminuria/therapy , Creatine/metabolism , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Period , Water-Electrolyte Balance
19.
Zhonghua Yi Xue Za Zhi ; 91(37): 2623-6, 2011 Oct 11.
Article in Zh | MEDLINE | ID: mdl-22321927

ABSTRACT

OBJECTIVE: To evaluate the values of serum level of B type natriuretic peptide level (BNP) in the prediction of fluid overloading after major abdominal operations. METHODS: The levels of BNP were dynamically monitored in 105 patients during peri-operative period from February 2009 to November 2010. Then comparisons were made with age and the volume of positive fluid balance. RESULTS: A post-operative elevation of BNP was observed in all cases. Among them, the peak level of BNP exceeded 100 ng/L in 32 patients while a normal peak level of BNP was found in 73 patients. Congestive heart failure (CHF) was diagnosed in 5 patients. At every single time point, the volume of positive fluid balance showed no significant difference among the peak level of BNP < 100 ng/L, ≥ 100 ng/L and CHF patients (all P > 0.05). In the group of peak level of BNP ≥ 100 ng/L, the patients received post-operative diuretic and the urine volume increased significantly [(280 ± 55) ml/h vs (82 ± 22) ml/h, P < 0.05]. However, in the group of the peak level of BNP < 100 ng/L, the urine volume showed no difference after dosing of diuretic [(95 ± 18) ml/h vs (89 ± 24) ml/h, P > 0.05]. Single variance analysis showed that the elevated level of BNP was associated with age and concurrent cardiopulmonary diseases (R = 0.87, P = 0.006) but not with the volume of positive fluid balance (R = 0.43, P = 0.080). And multiple variance analysis showed the similar results (R = 0.59, P = 0.020, R = 0.38, P = 0.120). In all cases, the levels of BNP peaked at 12 hours post-operation. However, body weight and the volume of positive fluid balance peaked at 18 - 24 hours post-operation. CONCLUSION: The post-operative level of BNP is associated with age. And a highly elevated level of BNP may predict the occurrence of fluid overloading. An early peak of BNP value may be used as a cut-off point of positive and negative fluid balances.


Subject(s)
Abdomen/surgery , Fluid Therapy/methods , Natriuretic Peptide, Brain/blood , Adult , Aged , Aged, 80 and over , Female , Humans , Intraoperative Period , Male , Middle Aged
20.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 23(3): 150-3, 2011 Mar.
Article in Zh | MEDLINE | ID: mdl-21366943

ABSTRACT

OBJECTIVE: To evaluate the effect of 7.5% hypertonic saline (HS) and 6% hydroxyethyl starch (HES) 130/0.4 on early fluid resuscitation for severe sepsis. METHODS: Prospective randomized control trial was carried out in intensive care unit (ICU) of the Affiliated Hospital of Jianghan University. One hundred and thirty five patients with severe sepsis were randomly divided into three groups, each group consisted of 45 patients. Patients in HS+HES group received lactated Ringer solution following 4 ml/kg of 7.5% HS and 6% HES 130/0.4 500 ml, those in HES group received lactated Ringer solution following 6% HES 130/0.4 500 ml, and those in the lactated Ringer group (RL group) received lactated Ringer solution only.Mean arterial pressure (MAP), oxygenation index (PaO2/FiO2),arterial lactate (Lac),lactate clearance rate, acute physiology and chronic health evaluation II(APACHEII) score,fluid infusion volume, urine output as well as incidence of multiple organ dysfunction syndrome (MODS), and mortality were compared among three groups at 6 hours and 24 hours after ICU admission. RESULTS: At 6 hours after ICU admission,MAP[mm Hg (1 mm Hg=0.133 kPa): 68.7 ± 3.0], PaO2/FiO2(mm Hg: 262.2 ± 17.4), lactate clearance rate [(21 ± 4)%] in HS+HES group were significantly higher than those in HES group [MAP: 63.8 ± 3.5,PaO(2)/FiO(2): 252.0 ± 21.2, lactate clearance rate: (11 ± 2)%] and RL group [MAP: 62.6 ± 3.6, PaO2/FiO2:248.4 ± 17.0,lactate clearance rate: (9 ± 1)%, all P <0.01]. Arterial Lac in HS+HES group (mmol/L: 3.5 ± 0.7) was significantly lower than that in HES group (4.1 ± 0.7) and RL group (4.0 ± 0.7, both P <0.01). There was no significant difference in APACHE II score between HS+HES group (13.2 ± 1.9) and HES group (14.0 ± 1.6), and the APACHEII score in HS+HES group was significantly lower than that in RL group (15.2 ± 1.7, P <0.01). At 24 hours after ICU admission, PaO2/FiO2 (mm Hg: 303.3 ± 17.3) was significantly higher in HS+HES group than that in HES group (282.9 ± 21.1) and RL group (268.9 ± 15.2, both P <0.01). There was no significant difference in MAP, arterial Lac, lactate clearance rate and APACHEII score among three groups. At 6 hours and 24 hours after ICU admission, fluid infusion volume in HS+HES group (ml, 6 hours: 1 877.8 ± 215.2, 24 hours: 5 475.6 ± 208.8) was markedly less than that in HES group (6 hours: 2 505.6 ± 276.2, 24 hours: 6 383.3 ± 287.4) and RL group (6 hours: 3 496.7 ± 325.5,24 hours: 7 439.6 ± 229.6), yet urine output in HS+HES group (ml, 6 hours: 294.2 ± 36.9, 24 hours : 2 793.8 ± 37.1) was significantly higher than that in HES group (6 hours: 248.9 ± 25.3, 24 hours : 2 248.9 ± 25.3) and RL group (6 hours: 178.9 ± 14.8, 24 hours: 2 000.4 ± 147.0, all P <0.01). The incidence of MODS in HS+HES group (6.7%) was statistically lower than that in RL group (28.9%, P <0.05), while no obvious difference was found between HS+HES group and HES group (17.8%, P >0.05). There was no significant difference in mortality among three groups (HS+HES group: 2.2%, HES group: 4.4%, RL group: 8.9%, all P >0.05). CONCLUSION: 7.5%HS and 6%HES 130/0.4 could improve the effect of early fluid resuscitation on severe sepsis, and it could lower the incidence of MODS.


Subject(s)
Hydroxyethyl Starch Derivatives/therapeutic use , Saline Solution, Hypertonic/therapeutic use , Sepsis/therapy , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Shock, Hemorrhagic
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