ABSTRACT
BACKGROUND: There are no universally accepted indications to initiate renal replacement therapy (RRT) among patients with acute kidney injury (AKI). This study aimed to develop a nomogram to predict the risk of RRT among AKI patients in intensive care unit (ICU). METHODS: In this retrospective cohort study, we extracted AKI patients from Medical Information Mart for Intensive Care III (MIMIC-III) database. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%). Multivariable logistic regression based on Akaike information criterion was used to establish the nomogram. The discrimination and calibration of the nomogram were evaluated by Harrell's concordance index (C-index) and Hosmer-Lemeshow (HL) test. Decision curve analysis (DCA) was performed to evaluate clinical application. RESULTS: A total of 7413 critically ill patients with AKI were finally enrolled. 514 (6.9%) patients received RRT after ICU admission. 5194 (70%) patients were in the training cohort and 2219 (30%) patients were in the validation cohort. Nine variables, namely, age, hemoglobin, creatinine, blood urea nitrogen and lactate at AKI detection, comorbidity of congestive heart failure, AKI stage, and vasopressor use were included in the nomogram. The predictive model demonstrated satisfying discrimination and calibration with C-index of 0.938 (95% CI, 0.927-0.949; HL test, P = 0.430) in training set and 0.935 (95% CI, 0.919-0.951; HL test, P = 0.392) in validation set. DCA showed a positive net benefit of our nomogram. CONCLUSION: The nomogram developed in this study was highly accurate for RRT prediction with potential application value.
Subject(s)
Acute Kidney Injury , Nomograms , Humans , Retrospective Studies , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Renal Replacement Therapy , Intensive Care UnitsABSTRACT
The taste is the quality attribute for the development and production of traditional Chinese medicine(TCM). To improve the medication compliance of the big brand TCM, Xiaoer Ganmao Oral Liquid, a correlation model between the electronic tongue sensor signal value and human sensory evaluation score was established, and an optimization strategy of taste improvement for Xiaoer Ganmao Oral Liquid was developed with the key techniques of statistical experimental design. Based on the above model, the optimal formulation was determined as follows: aspartame content of 1-2 mg·mL~(-1), acesulfame-K content of 1.5-3 mg·mL~(-1), and steviol glycoside content of 1-2 mg·mL~(-1). Furthermore, the optimal formulation was verified by human sensory evaluation. Therefore, the taste of Xiaoer Ganmao Oral Liquid was improved. Taking Xiaoer Ganmao Oral Liquid as an example, the present study developed the taste formulation optimization method based on the correlation between the electronic tongue and human sensory evaluation, which is expected to provide an important reference to improve the taste of oral liquid of TCM.
Subject(s)
Electronic Nose , Taste , Humans , Medicine, Chinese TraditionalABSTRACT
BACKGROUND: With the increasing prevalence of human immunodeficiency virus (HIV), the incidence of Mycobacterium tuberculosis (M. tuberculosis) bacteremia has also increased. As a common affliction of acquired immunodeficiency syndrome patients, M. tuberculosis infection is associated in these patients with severe sepsis and high mortality. In contrast, M. tuberculosis bacteremia is rarely seen in HIV-negative patients, and M. tuberculosis has never been reported from the blood of patients with liver cirrhosis. CASE SUMMARY: We evaluated a 55-year-old Chinese male patient who had been admitted to the hospital with abdominal distension of unknown cause of one-week duration, accompanied by diarrhea, shortness of breath, and occasional fever. Based on these indicators of abnormal inflammation and fever, we suspected the presence of an infection. Although evidence of microbial infection was not found in routine clinical tests and the patient did not show typical clinical symptoms of infection with M. tuberculosis, next-generation sequencing of blood samples nevertheless demonstrated the presence of M. tuberculosis, which was subsequently isolated from blood samples grown in conventional BacT/ALERT FA blood culture bottles. CONCLUSION: Our findings demonstrate that HIV-negative liver cirrhosis patients can also be infected with M. tuberculosis.
ABSTRACT
The spatial distribution uniformity of valuable medicines is the critical quality attribute in the process control of Tongren Niuhuang Qingxin Pills. With the real world sample of the mixed end-point powder of Tongren Niuhuang Qingxin Pills as the research object, hyperspectral imaging technology was used to collect a total of 32 400 data points with a size of 180 pix×180 pix. Spectral angle matching(SAM), classical least squares and mixed tuned matched filtering(MTMF) were used to identify the spatial distribution of rare medicines. MTMF model showed higher identification accuracy, therefore the spatial distribution of the blended intermediates was identified based on the MTMF model. The histogram method was also used to evaluate the spatial distribution uniformity of rare medicines. The results showed that the standard deviation was 4.78, 6.5, 3.48, 1.96, and 3.00 respectively for artificial bezoar, artificial musk, Borneol, Antelope horn and Buffalo horn; the variance was 22.8, 42.3, 12.1, 3.82, and 9.00, and the skewness was 1.26, 1.71, 0.06,-0.86, and 1.04, respectively. The final results showed that the most even blending was achieved in concentrated powder of Borneol, Antelope horn and Buffalo horn, followed by artificial bezoar, and last artificial musk. A visualization method was established for quality attributes of distribution uniformity in blending process of Tongren Niuhuang Qingxin Pills. It could provide evidences of quality control methods in the mixing process of big brand traditional Chinese medicine.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Powders , Quality ControlABSTRACT
Texture sensory attributes are the key items in quality control of Chinese medicinal honeyed pills. The purpose of this study is to develop a quality control method for assessing the texture sensory attributes of Chinese medicinal honeyed pills based on real-world Tongren Niuhuang Qingxin pilular masses and finished products. First, parameters of texture profile analysis(TPA) were optimized through single factor and central composite design(CCD) experiments to establish a detection method for texture sensory attri-butes of Tongren Niuhuang Qingxin Pills. The results showed that the established detection method was stable and reliable, with the optimal parameters set up as follows: deformation percentage of 70%, detection speed at 30 mm·min~(-1), and interval time of 15 s. Furthermore, 540 data points yielded form six texture sensory attributes of pills from 30 batches were subjected to multivariate statistical process control(MSPC) with Hotelling T~2 and squared prediction error(SPE) control charts to establish the quality control method of Tongren Niuhuang Qingxin Pills. This study is expected to provide a reference for improving the quality control system of Chinese medicinal honeyed pills.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Quality ControlABSTRACT
The physical properties of ginkgo leaves extract(GLE) are the critical quality attributes for the control of the manufacturing process of ginkgo leaves preparations. In this study, 53 batches of GLE with different sources from the real world were used as the objects to carry out the research from 3 levels. First, based on micromeritics evaluation method, a total of 29 physical attribute quality parameters in five dimensions were comprehensively characterized, with a total of 1 537 data points. Further, with use of physical fingerprinting technology combined with similarity evaluation, the powder physical properties of 53 batches of GLE showed obvious differences from an overall perspective, and the similarity of the physical fingerprints was 0.876 to 1.000. Secondly, hierarchical clustering analysis(HCA) and principal component analysis(PCA) models were constructed to realize the reliable identification and differentiation of real-world materials produced by GLE from different sources. Multivariate statistical process control(MSPC) model was used to create GLE material Hotelling T~2 and squared prediction error(SPE) control charts. It was found that the SPE score of B_(21) powder exceeded the 99% confidence control limit by 22.495 9, and the SPE scores of A_1 and C_(10) powder exceeded the 95% confidence control limit by 16.099 2, realizing the determination of abnormal samples in the materials of GLE from the production in real world. Finally, the physical quality control method of GLE in the production process of ginkgo leaves preparations was established in this study, providing a reference for the quality control methods of ginkgo leaves preparations in their manufacturing process.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Ginkgo biloba , Plant Extracts , Plant Leaves , Powders , Quality ControlABSTRACT
The physical properties of powder and granules are the critical quality attributes for the process control of Suhuang Zhike Capsules, a big brand traditional Chinese medicine. This paper took the production of 25 batches of real-world Suhuang Zhike Capsules dry extract powder and granules intermediates as the research object. Firstly, a method for testing the physical properties of Suhuang Zhike Capsules powder and granules with 19 physical indicators was established. The results showed that the granules of dry extract powder after granulation had a smaller particle size, wider particle size distribution range and poor fluidity, which easily caused the problem of over-limit capsule loading. Secondly, correlation analysis, principal component analysis and cluster analysis were used for mathematical statistics. The correlation analysis showed that the density of dry extract powder could affect the chroma and fluidity. At the same time, the particle size in the granules had a stronger effect on the chroma and fluidity than the density. The study also found that the particle size and hygroscopicity of dry extract powder were potentially key physical properties that affected the physical properties of granules. Furthermore, the results of principal component analysis and cluster analysis showed that the consistency of the physical properties between the dry extract powder and intermediate granules was relatively poor. To this end, similarity analysis was carried out, and the quality control method of powder and granules based on physical fingerprint was established. The results showed that the physical fingerprint similarity of 25 batches of dry extract powder was 0.639-0.976, and the physical fingerprint similarity of the gra-nules was 0.716-0.983. With the similarity of 0.85 as the threshold, the batches with abnormal physical properties could be identified. In this study, the process quality control method of Suhuang Zhike Capsules based on the physical properties of powder and granules was established finally, which realized the identification of abnormal batches, and provided a reference for the process quality control of Suhuang Zhike Capsules.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Capsules , Powders , Quality ControlABSTRACT
Assessment of the status property(boiling time) is a challenge for the quality control of extraction process in pharmaceutical enterprises. In this study, the pilot extraction process of Phellodendron chinense was used as the research carrier to develop an online near-infrared(NIR) quality control method based on the status property(boiling time). First, the NIR spectra of P. chinense were collected during the two pilot-scale extraction processes, and the status property(boiling time) was assessed by observing the state of bubbles in the extraction tank using a transparent window during the extraction process, which was then used as a reference standard. Based on the moving block standard deviation(MBSD) algorithm, the assessment model using online NIR spectra for boiling time during extraction process was established. In addition, the model was optimized as follows: standard normal variable(SNV) for spectral pretreatment, modeling band of 800-2 200 nm, and window size of 4. The results showed that, with 0.002 0 as the MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process. Furthermore, the principal component analysis-moving block standard deviation(PCA-MBSD) model was developed by our group to reduce the influence of online NIR spectral noise and background signal on the model, and the number of principal components was optimized into 2 in the PCA-MBSD model. The results showed that, with 0.000 075 as the PCA-MBSD model threshold, the boiling time can be accurately assessed using online NIR spectra during extraction process, with improved reliability. This study can provide a assessment method for boiling time during extraction process using online NIR spectra, which can replace the empirical judgment in manual observation, and realize the digitalization of the extraction process for big brand traditional Chinese medicine.
Subject(s)
Medicine, Chinese Traditional , Spectroscopy, Near-Infrared , Principal Component Analysis , Quality Control , Reproducibility of ResultsABSTRACT
[This corrects the article DOI: 10.1016/j.chmed.2018.12.004.].
ABSTRACT
Extracorporeal membrane oxygenation (ECMO) can provide respiratory and cardiac support to patients in reversible devastated conditions. Heparin is the mainstay for anticoagulation during ECMO. Bivalirudin, a direct thrombin blocker, may represent an effective alternative for patients suffering from heparin-induced thrombocytopenia (HIT). We present the first case of a Chinese patient who experienced HIT and received bivalirudin anticoagulation during ECMO. In addition, we present a systematic review for this topic. We searched PubMed, EMBASE, and Cochrane Library (up to April 20, 2020) for studies that included patients undergoing ECMO, presenting with HIT, requiring bivalirudin treatment, and reporting relevant outcomes. The literature review yielded 15 studies involving 123 patients, amongst whom 58 patients were confirmed or suspected HIT patients, and 76 patients received bivalirudin as an anticoagulant for ECMO. Twelve studies were included for quantitative synthesis, and 46 patients were retrieved. The mean age of these patients was 46 years, and 30 patients were males. The average maintenance rate of bivalirudin was 0.27 ± 0.37 mg/kg/h, in order to maintain a target of activated clotting time (ACT) of 160-220 s. Additionally, bivalirudin doses in patients with continuous renal replacement therapies (CRRT) and patients without CRRT were 0.15 ± 0.06 mg/kg/h vs 0.28 ± 0.36 mg/kg/h, respectively (p=0.15). Most of the patients with confirmed HIT improved platelet counts in 3.3 ± 2.8 days after switching to bivalirudin anticoagulation. The patient-level data showed that 29 cases survived, 1 reported major bleeding, and 4 reported thrombotic events. Bivalirudin might be a promising optimal choice for ECMO anticoagulation in patients with HIT. A tailored protocol for management of bivalirudin treatment during ECMO should be developed with caution. Further prospective studies are necessary to standardise the use of bivalirudin. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020160907.
ABSTRACT
Docosahexaenoic acid (DHA) is reported to have the potential to ameliorate pulmonary arterial hypertension (PAH), while the specific mechanism is still obscure. This study aims to investigate the function of DHA in pulmonary artery smooth muscle cells (PASMCs) and explore the underlying mechanism. In our study, DHA was used to incubate PASMCs. Cytosolic-free Ca2+ concentration ([Ca2+ ]cyt) was measured using Fluo-3 AM method. Real-time polymerase chain reaction was used to detect microRNA-16 (miR-16) and calcium-sensing receptor (CaSR) messenger RNA expression levels. CCK-8 assay, BrdU assay, and Transwell assay were employed to detect the effects of DHA on proliferation and migration of PASMCs. CaSR was confirmed as a direct target of miR-16 using dual-luciferase assay, polymerase chain reaction, and Western blot analysis. It was found that DHA significantly inhibited PASMC proliferation and migration and decreased [Ca2+ ]cyt. After transfection of miR-16 mimics, proliferation and migration ability of PASMCs were significantly inhibited, whereas opposite effects were observed after miR-16 inhibition. [Ca2+ ]cyt was also inhibited by miR-16 transfection. DHA then promoted the expression of miR-16, and the effects of DHA on PASMCs were annulled when miR-16 was inhibited. CaSR was identified as a direct target of miR-16. CaSR was inhibited directly by miR-16 and indirectly by DHA. In conclusion, DHA inhibits the proliferation and migration of PASMCs, and probably ameliorates PAH via regulating miR-16/CaSR axis.
Subject(s)
Calcium/metabolism , Down-Regulation/drug effects , MicroRNAs/metabolism , Muscle, Smooth/drug effects , Pulmonary Artery/drug effects , Receptors, Calcium-Sensing/metabolism , Binding Sites , Cells, Cultured , Docosahexaenoic Acids/pharmacology , Humans , Ion Transport , Muscle, Smooth/cytology , Muscle, Smooth/metabolism , Pulmonary Artery/cytology , Pulmonary Artery/metabolismABSTRACT
BACKGROUND: Kidney dysfunction frequently occurred after orthotopic liver transplantation (OLT). Chronic renal disease (CKD) is a complicated problem and is associated with increased mortality. The aim of this study is to find the risk factors for the incidence of CKD at 1 year after OLT in China. METHODS: From January 2017 to December 2017, we retrospectively assessed 280 recipients in our single center. Chronic renal failure was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for 3 months, regardless of the presence or absence of structural kidney damage. Cox proportional hazard model was used to identify the factors to the incidence of CKD after liver transplantations. Kaplan-Meier plots with log-rank test were presented to evaluate patient survival time in those with and without CKD. RESULTS: With a median follow-up of 17.4 months, 48 patients developed CKD after liver transplantations, representing 17.1% of the cohort. The cox-regression model showed that recipients age (HR = 1.097, P < 0.01), AKI (HR = 1.542, P < 0.01) and MELD score (HR = 1.077, P < 0.01) were significantly associated with the development of post-transplant CKD at 1 year. Recipient survival at 1 year was significantly worse in recipients with CKD compared to those without CKD (P < 0.01) after adjustment by age and gender. CONCLUSION: Our findings suggested that age, AKI and MELD score were associated with the incidence of CKD 1 year after OLT in a Chinese cohort. Recipients with CKD were associated with worse survival.
Subject(s)
End Stage Liver Disease/surgery , Liver Transplantation/adverse effects , Renal Insufficiency, Chronic/epidemiology , Acute Kidney Injury/epidemiology , Adult , Age Factors , Female , Glomerular Filtration Rate , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival RateABSTRACT
Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo. METHODS: In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12â¯h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated. RESULTS: We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM. CONCLUSION: Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner.
Subject(s)
Angiotensin II/pharmacology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Pancreas/injuries , Pancreas/pathology , Pancreatitis/therapy , Umbilical Cord/cytology , Acute Disease , Animals , Apoptosis/drug effects , Culture Media, Conditioned/pharmacology , Disease Models, Animal , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Models, Biological , Neovascularization, Physiologic/drug effects , Pancreas/drug effects , Pancreatitis/pathology , Paracrine Communication/drug effects , Rats , Vascular Endothelial Growth Factor Receptor-2/metabolismABSTRACT
OBJECTIVE: Inflammation correlates with delirium. Galectin-3 is a proinflammatory protein. This study aimed to determine relation of serum galectin-3 levels to delirium of postpartum intensive care unit (ICU) women. MATERIALS AND METHODS: In this prospective observational study, serum galectin-3, S100B, and C-reactive protein levels of 412 postpartum ICU women and 412 healthy women were measured. Delirium and Acute Physiology and Chronic Health Care Evaluation II (APCHCE II) scores were recorded. RESULTS: Serum levels of galectin-3, S100B, and C-reactive protein were significantly elevated in the postpartum women than in the healthy women. Galectin-3 levels were highly associated with APCHCE II scores and S100B and C-reactive protein levels. Galectin-3, C-reactive protein, and S100B levels and APCHCE II scores were identified as independent predictors for delirium. Area under the curve (AUC) of serum galectin-3 levels was similar to that of S100B levels, and significantly exceeded those of C-reactive protein levels and APCHCE II scores. Moreover, galectin-3 significantly improved the AUCs of APCHCE II scores, S100B levels, and C-reactive protein levels. CONCLUSIONS: Galectin-3, involved in inflammatory process underlying delirium-related brain injury, might be a potential biomarker to predict delirium of postpartum ICU women.
Subject(s)
Critical Illness , Delirium/blood , Galectin 3/blood , Inflammation/blood , Puerperal Disorders/blood , Adult , Biomarkers/blood , C-Reactive Protein , China , Delirium/genetics , Female , Galectin 3/genetics , Humans , Immunoassay , Intensive Care Units , Middle Aged , Prospective Studies , Young AdultABSTRACT
BACKGROUND Colorectal adenocarcinoma is the second leading cause of cancer-related death in the world. The stage of the disease is related to the survival of the patient, and in early phases surgery is the main modality of treatment. The main aim of modern medicinal chemistry is to synthesize small molecules via drug designing, especially by targeting tumor cells. MATERIAL AND METHODS A new series of 19 compounds containing benzothiazole and thiazole were designed. Molecular docking studies were performed on the designed series of molecules. Compounds showing good binding affinity towards the EGFR receptor were selected for synthetic studies. Characterization of the synthesized compounds was done by FTIR, 1HNMR, Mass and C, H, N, analysis. RESULTS The anticancer evaluation of the synthesized compounds was done at NIC, USA at a single dose against colon cancer cell lines HCT 116, HCT15, and HC 29. The active compounds were further evaluated for the 5-dose testing. Compounds were designed by using docking analysis. To ascertain the interaction of EGFR tyrosine kinase binding, energy calculation was used. CONCLUSIONS The results of the present study indicate that the designed compounds show good activity against colon cancer cell lines, which may be further studied to design new potential molecules.
Subject(s)
Colonic Neoplasms/pathology , Drug Design , Drug Screening Assays, Antitumor , Adenosine Triphosphate , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Dose-Response Relationship, Drug , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Molecular Docking SimulationABSTRACT
We report a novel ratiometric and reversible fluorescent probe for Cd(2+) detection utilizing a 6-(dimethylamino)quinaldine derivative as the fluorophore and a 2-hydrazinopyridine derivative as Cd(2+) chelator. This ratiometric fluorescent probe possesses favorable photophysical properties. It shows a large (55 nm) red-shift from 515 nm to 570 nm in the emission spectrum. Moreover, this probe also exhibits an excellent linear relationship of fluorescence intensity ratio (F570/F515) (R(2)=0.989) vs. Cd(2+) concentration in the range of 0-10 µM at physiological pH, which can serve as a "quantitative detecting" probe for Cd(2+). Utilizing this sensitive and selective probe, we have successfully detected Cd(2+) in living cells.
Subject(s)
Cadmium/analysis , Fluorescent Dyes/analysis , Fluorescent Dyes/chemistry , Methylamines/chemistry , Quinolines/chemistry , Cell Survival , Dose-Response Relationship, Drug , Fluorescent Dyes/chemical synthesis , HeLa Cells , Humans , Hydrogen-Ion Concentration , Methylamines/chemical synthesis , Methylamines/pharmacology , Molecular Structure , Pyridones/chemistry , Quantum Theory , Quinolines/chemical synthesis , Quinolines/pharmacology , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
A series of aryl-2H-pyrazole derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro as potent xanthine oxidase inhibitors. Among them, 2 aryl-2H-pyrazole derivatives showed significant inhibitory activities against xanthine oxidase. Compound 19 emerged as the most potent xanthine oxidase inhibitor (IC50=9.8 µM) in comparison with allopurinol (IC50=9.5 µM). The docking study revealed that compound 19 might have strong interactions with the active site of xanthine oxidase. This compound is thus a new candidate for further development for the treatment of gout.
Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Pyrazoles/chemistry , Pyrazoles/pharmacology , Xanthine Oxidase/antagonists & inhibitors , Animals , Catalytic Domain/drug effects , Cattle , Enzyme Inhibitors/chemical synthesis , Molecular Docking Simulation , Pyrazoles/chemical synthesis , Structure-Activity Relationship , Xanthine Oxidase/chemistry , Xanthine Oxidase/metabolismABSTRACT
The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.
Subject(s)
Dietary Fats/toxicity , Dietary Sucrose/toxicity , Fructose/toxicity , Non-alcoholic Fatty Liver Disease/chemically induced , Toll-Like Receptor 4/metabolism , Activins/genetics , Activins/metabolism , Animals , Dietary Fats/administration & dosage , Dietary Sucrose/administration & dosage , Fructose/administration & dosage , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factor-7/genetics , Interferon Regulatory Factor-7/metabolism , Mice , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Signal Transduction , Toll-Like Receptor 4/genetics , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To explore the related factors of remission and relapse in lupus nephritis (LN) patients. METHODS: A retrospective study was conducted for proliferation and membrane LN patients diagnosed from 2003 to 2010. Their clinical, laboratory and pathological parameters were collected. According to the response to treatment, they were divided into 3 groups of complete remission (CR), partial remission (PR) and no response (NR). Those in remission were divided into 2 groups of relapsing and non-relapsing during maintenance period. Associated factors for remission and relapse were analyzed. RESULTS: (1) Among a total of 105 patients, there were 99 females and 6 males with an average follow-up period of (51 ± 30) months. Eighty-six patients achieved remission after 6-month treatment. (2) The outcomes were CR (n = 36), PR (n = 50) and NR (n = 19). Proteinuria in PR group was higher than that in CR group (4.7 (3.1-7.6) vs 1.7 (1.4-3.8), P < 0.01) while proteinuria of CR group was lower than that of NR group (1.7 (1.4-3.8) vs 3.0 (2.3-5.9), P < 0.01). Serum albumin level of CR group was significantly higher than those of PR (30.6 (27.8-34.6) vs 22.4 (19.3-29.4), P < 0.01) and NR groups (30.6 (27.8-34.6) vs 23.1 (18.9-28.6), P < 0.01). Serum creatinine was significantly higher in NR group than those of CR (128.9 (69.9-184.3) vs 58.1 (53.0-70.9), P < 0.01) and PR group (128.9 (69.9-184.3) vs 67.5 (53.5-129.1), P < 0.05). Acute index (AI) and chronic index (CI) were lower in CR group than those of PR and NR groups. (3) A total of 86 cases achieved remission (CR/PR) while 20 cases (23.3%) had relapse. During the maintenance period, the relapse rate was higher in the group on prednisone alone than those on combined therapy of prednisone plus immunosuppressant (P < 0.05). Sixty patients (90.9%) in non-relapse group and 12 cases (60.0%) in recurrence group had good compliance. CONCLUSIONS: Initial proteinuria, serum creatinine, serum albumin, estimated glomerular filtration rate and AI were related with remission of induction period. Prednisone-alone therapy is an independent risk factor for relapse during maintenance period. Poor compliance of patients may be one of the risk factors for relapse during maintenance period. It may be useful to maintain sustained remission and reduce relapse in LN patients by improving their compliance and using steroids plus immunosuppressant during maintenance period.