Systematic Optimization of Universal Real-Time Hypersensitive Fast Detection Method for HBsAg in Serum Based on SERS.

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.

Co-encapsulation of curcumin and anthocyanins in bovine serum album-fucoidan nanocomplex with a two-step pH-driven method.

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. CONCLUSION: In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.

CD39 identifies a specific CD8 + T cell population in lung adenocarcinoma-related metastatic pleural effusion.

Malignant pleural effusion (MPE), which is a complex microenvironment that contains numerous immune and tumour signals, is common in lung cancer. Gene alterations, such as driver gene mutations, are believed to affect the components of tumour immunity in the microenvironment (TIME) of non-small-cell lung cancer. In this study, we have shown that pleural CD39 + CD8 + T cells are selectively elevated in lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFRwt) compared to those with newly diagnosed mutant EGFR (EGFRmu). Furthermore, these CD39 + CD8 + T cells are more prevalent in MPE with acquired resistance to EGFR-tyrosine kinase inhibitors (AR-EGFR-TKIs). Our analysis reveals that pleural CD39 + CD8 + T cells exhibit an exhausted phenotype while still retaining cytolytic function. Additionally, they have a higher T cell receptor (TCR) repertoire clonality compared to CD39-CD8 + T cells, which is a unique characteristic of LUAD-related MPE. Further investigation has shown that TCR-Vß clonality tends to be more enhanced in pleural CD39 + CD8 + T cells from MPE with AR-EGFR-TKIs. In summary, we have identified a subset of CD8 + T cells expressing CD39 in MPE, which may potentially be tumour-reactive CD8 + T cells. This study provides new insights into the dynamic immune composition of the EGFRmu tumour microenvironment.

MicroRNA Imaging Encounters Rolling Circle Amplification: Intracellular Na+-Fueled Linear Programmable DNAzyme Nanostructure.

DNAzyme motors are widely used for the sensitive detection of intracellular miRNAs due to their excellent signal response. Generally, the addition of exogenous mental ions to DNAzyme motors is crucial for the efficient operation of the system. Moreover, the position of the DNAzyme relative to the substrate has a significant impact on the cleavage rate during the reaction. Herein, we proposed a highly loaded Na+-fueled linear programmable DNAzyme nanostructure (LPDN) composed of long, single-strand DNA produced by rolling circle amplification reactions that served as binding partners for Na+-specific DNAyme and substrate. In the meantime, the long, programmable scaffolds can precisely control the position of the DNAzyme and substrate for the optimal effect. During the assay, miR-21 and endogenous Na+ can specifically trigger multiple adjacent substrate-cleaving reactions, resulting in a significant recovery of the Cy3 fluorescence signal in living cells. This method could enable in situ real-time imaging and biocompatibility-enhancing evaluation of intracellular miR-21-level changes. Furthermore, LPDN's ability to distinguish normal cells from cancer cells makes it a promising candidate for early cancer diagnosis and imaging analysis of cancer.

[Medical visit status and clinical features in patients with IgG4 related disease].

OBJECTIVE: To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments. METHODS: A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized. RESULTS: A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%). CONCLUSION: IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

[Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages].

OBJECTIVE: To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages. METHODS: In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table. RESULTS: Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-ß2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%. CONCLUSION: Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

[Evaluation methods of clinical efficacy of traditional Chinese medicine].

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

[Bone marrow mesenchymal stem cell-derived exosomes protect TM3 Leydig cells from cyclophosphamide-induced injury].

OBJECTIVE: To investigate the effect of exosomes derived from mouse bone marrow mesenchymal stem cells (BMSC) on the injury of TM3 Leydig cells induced by cyclophosphamide (CP). METHODS: The exosomes from BMSCs were extracted by ultrahigh speed centrifugation, and their particle size and morphology observed under the electron microscope, and their typical marker proteins examined by Western blot. The uptake of exosomes by TM3 Leydig cells was observed by co-culturing the exosomes with the TM3 cells. The viability and apoptosis rate of the TM3 cells in the normal control, CP-induction and CP+exosomes groups were detected using the CCK-8 method and flow cytometry respectively. ELISA was used to measure the testosterone (T) level in the cell supernatant, and Western blot adopted to determine the expression level of the steroidogenic acute regulatory (StAR) protein, a key enzyme related to T synthesis. RESULTS: The viability of the TM3 Leydig cells was markedly decreased and the apoptosis rate of the cells remarkably increased in the CP-induction group compared with that in the normal control, but both significantly restored after co-culture with exosomes (P < 0.01 and P < 0.05). The T level in the supernatant and the expression of the StAR protein in the cells were lower in the CP-induction than in the normal control group, but both dramatically increased in the CP+exosomes group (P < 0.01). CONCLUSION: Exosomes from BMSCs and protect TM3 Leydig cells from cyclophosphamide-induced injury and restore the level of testosterone secreted by the TM3 cells to a certain extent.

[Effects of silencing the SEMG1 protein on the cycle and apoptosis of GC-1 spg cells].

OBJECTIVE: To investigate the effects of silencing the semenogelin 1 (SEMG1) protein on the cycle and apoptosis of the spermatogonia germ cell line (GC-1 spg). METHODS: SEMG1-specific siRNA was transfected into GC-1 spg cells by lipofectamine 2000 (the siRNA-SEMG1 group), the relative expression levels of the SEMG1 protein in the GC-1 spg cells of the siRNA-SEMG1, blank control and negative control groups were detected by Western blot, and the apoptosis and cycle of the cells in different groups were determined by flow cytometry. RESULTS: The expression of the SEMG1 protein in the GC-1 spg cells was dramatically decreased in the siRNA-SEMG1 group compared with those in the blank and negative control groups (1.80±0.05 vs 2.51±0.13 and 2.50±0.12， P < 0.01), but the apoptosis rate was remarkably higher in the former than in the latter two groups (ï¼»6.77 ± 0.15ï¼½% vs ï¼»0.70 ± 0.06ï¼½% and ï¼»0.8 ± 0.06ï¼½%, P < 0.01). No statistically significant difference was observed in the cell cycles among the three groups (P > 0.05). In addition, Western blot showed that the expression of the caspase-3 protein was significantly higher and that of the BCL2 protein markedly lower in the siRNA-SEMG1 than in the blank and negative control groups (P < 0.05). CONCLUSIONS: SEMG1-specific siRNA can effectively silence the expression of the SEMG1 protein in GC-1 spg cells and promote their apoptosis.

[Efficacy and safety of vitamin D as adjuvant therapy for childhood pneumonia: a Meta analysis].

OBJECTIVE: To study the efficacy and safety of vitamin D as an adjuvant therapy for childhood pneumonia through a systematic review. METHODS: Cochrane Library, PubMed, EMbase, CNKI, Wanfang Data, and Weipu Data were searched for randomized controlled trials (RCTs) of vitamin D as the adjuvant therapy for childhood pneumonia published up to August 2019. Literature screening, quality assessment, and data extraction were performed based on inclusion and exclusion criteria. Revman 5.3 was used to perform the Meta analysis of outcome indicators. RESULTS: A total of 7 RCTs with 1 527 children were included, with 762 children in the vitamin D adjuvant therapy group and 765 children in the control group. The results of the Meta analysis showed that vitamin D adjuvant therapy had no effect on recovery time (P=0.67), length of hospital stay (P=0.73), and time to relief of fever (P=0.43). Furthermore, it did not reduce the recurrence rate (P=0.14), rate of adverse events (P=0.20), and mortality rate (P=0.98) of childhood pneumonia. CONCLUSIONS: Current evidence shows that vitamin D adjuvant therapy has no marked efficacy in the treatment of childhood pneumonia.

Phenotypes of the inflammatory cells in the induced sputum from young children or infants with recurrent wheezing.

BACKGROUND: To identify inflammatory cell types by phenotypic analysis of the inflammatory cells in the induced sputum. METHODS: This retrospective study included 1232 children and infants, who were assigned into mild/moderate groups (326) and severe group (602) by clinical symptom scores. Phenotypes of sputum inflammatory cells were analyzed using liquid-based thin-cytologic test and eosinophil-derived neurotoxin (EDN) was quantified by ELISA. RESULTS: Blood eosinophil count, serum total IgE level, and allergen detection rate were significantly higher in the severe group. In the 905 cases of qualified sputum, 526 cases exhibited at least one type of inflammatory cells, including neutrophil (343, 65.2%), eosinophil (161, 30.6%), and mixed granulocytes (22, 4.2%). Levels of neutrophils and eosinophils were significantly higher in the severe group than mild/moderate group, and eosinophil was predominant in the severe group. Serum EDN was 104.8 ± 39.4 µg/l in the eosinophil phenotype group, 112.6 ± 41.2 µg/l in the mixed group, 88.2 ± 36.6 µg/l in the neutrophil phenotype group, and 60.9 ± 34.6 µg/l in the paucigranulocytic phenotype group. CONCLUSION: Induced-sputum inflammatory cell count may be used to determine phenotype of wheezing. The criteria of classifying adult asthma could be applicable for children and infants.

Effects of large gradient high magnetic field (LG-HMF) on the long-term culture of aquatic organisms: Planarians example.

Large gradient high magnetic field (LG-HMF) is a powerful tool to study the effects of altered gravity on organisms. In our study, a platform for the long-term culture of aquatic organisms was designed based on a special superconducting magnet with an LG-HMF, which can provide three apparent gravity levels (µ g, 1 g, and 2 g), along with a control condition on the ground. Planarians, Dugesia japonica, were head-amputated and cultured for 5 days in a platform for head reconstruction. After planarian head regeneration, all samples were taken out from the superconducting magnet for a behavioral test under geomagnetic field and normal gravity conditions. To analyze differences among the four groups, four aspects of the planarians were considered, including head regeneration rate, phototaxis response, locomotor velocity, and righting behavior. Data showed that there was no significant difference in the planarian head regeneration rate under simulated altered gravity. According to statistical analysis of the behavioral test, all of the groups had normal functioning of the phototaxis response, while the planarians that underwent head reconstruction under the microgravity environment had significantly slower locomotor velocity and spent more time in righting behavior. Furthermore, histological staining and immunohistochemistry results helped us reveal that the locomotor system of planarians was affected by the simulated microgravity environment. We further demonstrated that the circular muscle of the planarians was weakened (hematoxylin and eosin staining), and the epithelial cilia of the planarians were reduced (anti-acetylated tubulin staining) under the simulated microgravity environment. Bioelectromagnetics. 2018;39:428-440. © 2018 Wiley Periodicals, Inc.

Geraniin induces apoptosis of human breast cancer cells MCF-7 via ROS-mediated stimulation of p38 MAPK.

Geraniin, a typical ellagitannin isolated from Phyllanthus urinaria Linn, has been found to possess a range of bioactive properties. In the present study, we found that Geraniin showed potent anti-proliferative effects on human breast cancer MCF-7 cells. The IC50 values were 9.94, 17.98 and 42.32 µM after 72-, 48- and 24-h treatment, respectively. Meanwhile, Geraniin could remarkably disrupt mitochondrial membrane potential and arrest S phase cell cycle. Western-blot analysis showed that Geraniin induced phosphorylation of the anti-apoptotic Bcl-2, and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3 in MCF-7 cells. Moreover, Geraniin treatment activated p38 mitogen-activated protein kinase (p38 MAPK) and the effect was blunted in MCF-7 cells with the treatment of a specific p38 inhibitor SB203580. Geraniin could generate intracellular reactive oxygen species (ROS), activate p38 MAPK then induce the apoptosis in MCF-7 cells, such phenomena was abrogated by pretreatment with N-acetyl-l-cysteine. In general, these results support the conclusion that Geraniin-induced apoptosis is mediated via ROS-mediated stimulation of p38 MAPK signaling.

Cross-Domain Feature Disentanglement for Interpretable Modeling of Tumor Microenvironment Impact on Drug Response.

High-throughput screening technology has enabled the generation of large-scale drug responses across hundreds of cancer cell lines. There remains a significant gap between in vitro cell lines and actual tumors in vivo in terms of their response to drug treatments yet. This is because tumors consist of a complex cellular composition and histopathology structure, known as the tumor microenvironment (TME), which greatly impacts the drug cytotoxicity against tumor cells. To date, no study has focused on modeling the impact of the TME on clinical drug response. In this study, we postulated that the intricate complexity of an actual tumor can be conceptually simplified into two separable components: cancerous cells and the tumor microenvironment. This assumption allowed us to model the influence of these two constituent parts on drug response through feature disentanglement. We employed a domain adaptation network to decouple and extract features from tumor transcriptional profiles. Specifically, two denoising autoencoders were separately used to extract features from cell lines (source domain) and tumors (target domain) for partial domain alignment and feature decoupling. The private encoder was enforced to extract information only about the TME. Moreover, to ensure generalizability to novel drugs, we employed a graph attention network to learn the latent representation of drugs, enabling us to linearly model the drug perturbation on cellular state in latent space. We validated our model on a benchmark dataset and demonstrated its superior performance in predicting clinical drug response and dissecting the influence of the TME on drug efficacy.

Invasive pulmonary and central nervous system aspergillosis in a child: A case report and literature review.

RATIONALE: Children with haematological malignancies have a higher risk of developing aggressive pulmonary aspergillosis and a higher mortality rate. The most common site of extrapulmonary aspergillosis in children is the central nervous system (CNS), and the death rate is higher when CNS is affected. Therefore, early diagnosis and treatment of invasive aspergillosis are essential for reducing mortality. PATIENT CONCERNS: We report a case of an 8-year-old girl with acute lymphoblastic leukaemia who developed invasive pulmonary aspergillosis complicated by CNS aspergillosis. Aspergillus was confirmed by metagenomic sequencing of pathogenic microorganisms. DIAGNOSES: Invasive pulmonary and central nervous system aspergillosis. INTERVENTIONS: The patient was treated with combined systemic antifungal agents (voriconazole and liposomal amphotericin B) and intrathecal injection of amphotericin B. OUTCOMES: The treatment was well tolerated and resulted in remarkable clinical and radiological head improvements. LESSONS: Invasive aspergillosis has a high mortality rate and requires early diagnosis and treatment. Pathogenic microbial metagenomic sequencing is a convenient method to assist in the early diagnosis of aspergillosis. Voriconazole is the drug of choice for the treatment of invasive aspergillosis. When CNS aspergillosis occurs, it can be combined with other systemic antifungal drugs and intrathecal injection of amphotericin B.

Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS: The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.

AOPPs induce MCP-1 expression by increasing ROS-mediated activation of the NF-κB pathway in rat mesangial cells: inhibition by sesquiterpene lactones.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays an important role in extracellular matrix accumulation through macrophage recruitment and activation in the development and progression of diabetic nephropathy. Therefore, this study examined whether advanced oxidation protein products (AOPPs) are involved in nuclear factor-κB (NF-κB) activation and MCP-1 mRNA and protein expression in mesangial cells (MCs) and evaluated the effects of derivatives of sesquiterpene lactones (SLs) on AOPP-induced renal damage. METHODS: MCP-1 mRNA and protein expression in MCs were determined by quantitative real-time PCR and ELISA, respectively. The level of intracellular reactive oxygen species (ROS) was determined by flow cytometry. The protein expression of tubulin, P47, NF-κB p65, phospho-NF-κB p65, IκB, phospho-IκB, IKKß and phospho-IKKß was evaluated by Western blot. RESULTS: AOPPs caused oxidative stress in MCs and activated the NF-κB pathway by inducing IκBα phosphorylation and degradation. Inhibition of ROS by SOD (ROS inhibitor) blocked the AOPP-mediated NF-κB pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP-1 mRNA and protein was associated with inhibition of IκBα degradation by SLs. CONCLUSION: AOPPs induce MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by SLs. These findings may provide a novel approach to treat inflammatory and immune renal diseases, including diabetic nephropathy.

Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-ß1 expression in rat mesangial cells.

Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-ß1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-ß1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-ß1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.

[Effects of linggui zhugan decoction combined calorie restriction on the insulin resistance of model rats and mechanisms research].

OBJECTIVE: To explore the effects of Linggui Zhugan Decoction (LZD) combined calorie restriction on fasting plasma glucose (FPG), the insulin resistance (IR), and the peroxisome proliferator-activated receptor gamma (PPAR-gamma) of IR model rats. METHODS: Totally 48 male Wistar rats were randomly divided into the control group, the model group, the calorie restriction group, and the TCM + calorie restriction group, 12 in each group. Ordinary forage was given to those in the control group, and high fat diet was fed to those in the rest 3 groups for 12 weeks to establish the IR model. After successful modeling, rats in the control group and the model group were continually fed with the original farage for 4 days. The normal saline at the daily dose of 20 mL/kg was given to them by gastrogavage. The normal saline at the daily dose of 20 mL/kg was given to rats in the calorie restriction group by gastrogavage after 4-day calorie restriction. LZD at the daily dose of 20 mL/kg was given to rats in the TCM +calorie restriction group by gastrogavage after 4-day calorie restriction. The body weight, FPG, serum fasting insulin (FINS), insulin resistance index (IRI), and the protein expression of PPAR-y in the omental adipose tissue were compared. RESULTS: After 4-day calorie restriction, the body weight obviously decreased in the calorie restriction group and the TCM +calorie restriction group, when compared with the model group (P <0.01). There was no statistical difference between the former two groups (P >0.05). The FINS and IRI obviously decreased in the calorie restriction group (P <0.01, P <0.05). The FPG, FINS, and IRI significantly decreased in the TCM + calorie restriction group (P <0. 05, P <0.01). The protein expression of PPAR-gamma obviously decreased in the calorie restriction group and the TCM + calorie restriction group (P <0.01).The phlegm dampness state was alleviated, with more significant effects shown in the TCM + calorie restriction group. CONCLUSIONS: LZD combined calorie restriction could reduce the body weight, FPG, and IRI of IR rats. Besides, it showed better effects than calorie restriction alone. Its effects in improving IR might be correlated with inhibiting the activities of PPAR-gamma. Meanwhile, it might play a role in inhibiting the differentiation of fat cells.