The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.

[Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea].

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

[Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation].

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(ß-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Effect of Wuzi Yanzong prescription on oligoasthenozoospermia rats based on UPLC-Q-TOF-MS metabolomics.

CONTEXT: Wuzi Yanzong Prescription (WYP) has long been used to treat male infertility, with convincing clinical evidence. However, its mechanism of action is not clear. OBJECTIVE: WYP chemical components were quantified by HPLC, and the effect on oligoasthenozoospermia rats was explored based on UPLC-Q-TOF-MS metabonomics technology. MATERIALS AND METHODS: The solution was extracted by alcohol and water; the content of eight components in the extracting solution was determined by HPLC. Twenty-four Sprague-Dawley rats were randomly divided into control (CG), model (MG) and administration (PG) groups. Oligoasthenozoospermia was induced for 30 days in all, but the CG with daily oral doses of 20 mg/kg Tripterysium glycosides (TG). PG was given daily oral doses of WYP solution (1.08 g/kg), CG and MG received the same volume of distilled water, all administered for 30 days. After the last administration, the serum samples were collected and detected by UPLC-Q-TOF-MS. RESULTS: An HPLC method for simultaneous determination of chlorogenic acid (0.081%), ellagic acid (0.021%), hyperoside (0.032%), verbascoside (0.011%), isoquercitrin (0.041%), astragalin (0.026%), kaempferol (0.009%) and schisandrin (0.014%) was established. Moreover, the 74 potential biomarkers and eight metabolic pathways related to oligoasthenozoospermia were identified by multivariate analysis and metabolite profiling. WYP can regulate 36 markers, mainly involving amino acid metabolism, lipid metabolism and nucleotide metabolism. DISCUSSION AND CONCLUSIONS: This is a simple and accurate method for quality control of WYP. It further enriches the potential mechanism of WYP in the treatment of oligoasthenozoospermia. It can provide a theoretical basis for the rational application of WYP.

Quantum Battery Based on Hybrid Field Charging.

A quantum battery consisting of an ensemble two-level atom is investigated. The battery is charged simultaneously by a harmonic field and an electrostatic field. The results show that the hybrid charging is superior to the previous case of only harmonic field charging in terms of battery capacity and charging power, regardless of whether the interaction between atoms is considered or not. In addition, the repulsive interaction between atoms will increase the battery capacity and charging power, while the attractive interaction between atoms will reduce the battery capacity and discharge power.

Multiple pulmonary cavities in an immunocompetent patient: a case report and literature review.

Legionella pneumonia (LP) is a relatively uncommon yet well-known type of atypical community-acquired pneumonia (CAP). It is characterized by a rapid progression to severe pneumonia and can be easily misdiagnosed. In most patients, chest computed tomography (CT) showed patchy infiltration, which may progress to lobar infiltration or even lobar consolidation. While pulmonary cavities are commonly observed in immunocompromised patients with LP, they are considered rare in immunocompetent individuals. Herein, we present a case of LP in an immunocompetent patient with multiple cavities in both lungs. Pathogen detection was performed using metagenomic next-generation sequencing (mNGS). This case highlights the unusual radiographic presentation of LP in an immunocompetent patient and emphasizes the importance of considering LP as a possible diagnosis in patients with pulmonary cavities, regardless of their immune status. Furthermore, the timely utilization of mNGS is crucial for early pathogen identification, as it provides multiple benefits in enhancing the diagnosis and prognosis of LP patients.

Machine learning-based radiomics strategy for prediction of acquired EGFR T790M mutation following treatment with EGFR-TKI in NSCLC.

The epidermal growth factor receptor (EGFR) Thr790 Met (T790M) mutation is responsible for approximately half of the acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. Identifying patients at diagnosis who are likely to develop this mutation after first- or second-generation EGFR-TKI treatment is crucial for better treatment outcomes. This study aims to develop and validate a radiomics-based machine learning (ML) approach to predict the T790M mutation in NSCLC patients at diagnosis. We collected retrospective data from 210 positive EGFR mutation NSCLC patients, extracting 1316 radiomics features from CT images. Using the LASSO algorithm, we selected 10 radiomics features and 2 clinical features most relevant to the mutations. We built models with 7 ML approaches and assessed their performance through the receiver operating characteristic (ROC) curve. The radiomics model and combined model, which integrated radiomics features and relevant clinical factors, achieved an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.79-0.81) and 0.86 (0.87-0.88), respectively, in predicting the T790M mutation. Our study presents a convenient and noninvasive radiomics-based ML model for predicting this mutation at the time of diagnosis, aiding in targeted treatment planning for NSCLC patients with EGFR mutations.

IgG4-related diseases involving pleura: a case report and literature review.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease with the potential to involve virtually all organs, including the pancreas, kidneys, lungs, and pleura, amongst others. IgG4-RD pleural involvement may cause diverse complications such as pleural effusion, pleural thickening, pleural nodules, and additional lesions, which can be presented in many clinical diseases. However, isolated cases of pleurisy are still rare in IgG4-RD. We report a 72-year-old patient who was admitted to our hospital with cough, expectoration, and fatigue. He had a right-sided pleural effusion, and the tissue evaluation of the pleural biopsy by medical thoracoscopy met the diagnostic criteria of IgG4-RD. His serum IgG4 levels were elevated and he was finally diagnosed with IgG4-RD pleural involvement. He was subsequently started on prednisone 40 mg daily and his pleural effusion was almost disappeared 2 weeks later. This paper reported a case of IgG4-RD who had exclusive involvement of the pleura and highlighted the significance of considering IgG4-RD as a potential diagnosis in patients with unexplained pleural effusion.

Semaphorin 7a aggravates TGF-ß1-induced airway EMT through the FAK/ERK1/2 signaling pathway in asthma.

Background: TGF-ß1 can induce epithelial-mesenchymal transition (EMT) in primary airway epithelial cells (AECs). Semaphorin7A (Sema7a) plays a crucial role in regulating immune responses and initiating and maintaining transforming growth factor ß1 TGF-ß1-induced fibrosis. Objective: To determine the expression of Sema7a, in serum isolated from asthmatics and non-asthmatics, the role of Sema7a in TGF-ß1 induced proliferation, migration and airway EMT in human bronchial epithelial cells (HBECs) in vitro. Methods: The concentrations of Sema7a in serum of asthmatic patients was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Sema7a and integrin-ß1 were examined using conventional western blotting and real-time quantitative PCR (RT-PCR). Interaction between the Sema7a and Integrin-ß1 was detected using the Integrin-ß1 blocking antibody (GLPG0187). The changes in EMT indicators were performed by western blotting and immunofluorescence, as well as the expression levels of phosphorylated Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) were analyzed by western blot and their mRNA expression was determined by RT-PCR. Results: We described the first differentially expressed protein of sema7a, in patients with diagnosed bronchial asthma were significantly higher than those of healthy persons (P<0.05). Western blotting and RT-PCR showed that Sema7a and Integrin-ß1 expression were significantly increased in lung tissue from the ovalbumin (OVA)-induced asthma model. GLPG0187 inhibited TGF-ß1-mediated HBECs EMT, proliferation and migration, which was associated with Focal-adhesion kinase (FAK) and Extracellular-signal-regulated kinase1/2 (ERK1/2) phosphorylation. Conclusion: Sema7a may play an important role in asthma airway remodeling by inducing EMT. Therefore, new therapeutic approaches for the treatment of chronic asthma, could be aided by the development of agents that target the Sema7a.

Ligustri Lucidi Fructus, a traditional Chinese Medicine: Comprehensive review of botany, traditional uses, chemical composition, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustri Lucidi Fructus (LLF) is one of the usual Chinese herbs that has long been used with high therapeutic and condition value. LLF is used for the treatment of dizziness and tinnitus, soreness and weakness of the waist and knees, premature greying of the hair, the darkness of the eyes, internal heat and thirst, bone steam and hot flashes and other symptoms. AIM OF THE STUDY: This review reviews botany, traditional uses, processing, phytochemistry, quality control, pharmacology, toxicity and pharmacokinetics to better understand its therapeutic potential. MATERIALS AND METHODS: The literature on LLF was obtained from Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WAN FANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. Phytochemical constituents' structures were drawn by ChemDraw software. RESULTS: So far, Multiple chemical components were isolated and identified from LLF, mainly including terpenoids and flavonoids. Modern studies have shown that LLF extracts and compounds have a wide range of pharmacological effects, including antitumor, liver protection, blood glucose, lipid-lowering, immune regulation, and other aspects. CONCLUSIONS: LLF occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant and its chemical composition, pharmacological activity, quality control, toxicity and pharmacokinetics.

Research progress on the treatment of epilepsy with traditional Chinese medicine.

BACKGROUND: Traditional Chinese Medicine (TCM) system is a medical system that has been expanding for thousands of years that was formed by the extensive clinical practice experience of many physicians and the accumulation of personal medication habits in China. In TCM, there is a history of long-term medication for epilepsy, the main treatment for epilepsy is TCM drugs and its prescription, supplemented by TCM modalities such as acupuncture therapy, moxibustion therapy, tuina, emotion adjustment therapy, etc. PURPOSE: With the modernization of TCM, the active ingredients and molecular mechanisms of TCM for epilepsy treatment have been gradually revealed. This review aimed to comprehensively summarize the TCM treatment of epilepsy, focusing on the current TCM drugs and some TCM formulae for the treatment of epilepsy, and to discuss the research progress of TCM for the treatment of epilepsy, and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: The mechanism of action of antiepileptic drugs (AEDs) was interpreted from different perspectives by searching online databases and querying various materials identify drugs used in both modern medicine and TCM systems for the treatment of epilepsy. We collected all relevant TCM for epilepsy literature published in the last 30 years up to December 2022 from electronic databases such as PubMed, CNKI and Web of Science, and statistically analyzed the literature for the following keyword information. The search terms comprise the keywords "TCM", "phytochemistry", "pharmacological activity", "epilepsy" and "traditional application" as a combination. Scientific plant names were provided by "The Plant List" (www.theplantlist.org). RESULTS: Epilepsy is a complex and serious disease of the brain and nervous system. At present, the treatment of epilepsy in modern medicine is mainly surgery and chemotherapy, but there are many serious side effects. By summarizing the treatment of epilepsy in TCM, it is found that there are various methods to treat epilepsy in TCM, mainly TCM drugs and its formulae. Many TCM drugs have antiepileptic effects. Now found that the main effective TCM drugs for the treatment of epilepsy are Curcumae Longae Rhizoma, Scorpio, Acori Tatarinowii Rhizoma, Uncariae Ramulus Cum Uncis and Ganoderma, etc. And the main compounds that play a role in the treatment of epilepsy are curcumin, gastrodin, ligustrazine, baicalin and rhynchophylline, etc. These TCM drugs have played an important role in the treatment of epilepsy in TCM clinic. However, the chemically active components of these TCM drugs are diverse and their mechanisms of action are complex, which are not fully understood and need to be further explored. CONCLUSIONS: TCM treats epilepsy in a variety of ways, and with the discovery of a variety of potential bioactive substances for treatment of epilepsy. With the new progress in the research of other TCM treatment methods for epilepsy, TCM will have greater potential in the clinical application of epilepsy.

Interleukin­27 ameliorates allergic asthma by alleviating the lung Th2 inflammatory environment.

Interleukin (IL)­27 can inhibit the differentiation of Th2 cells and plays a role in the development of asthma. However, whether the therapeutic administration of IL­27 in a mouse model of asthma can inhibit allergic responses remains a matter of debate. Additionally, the mechanisms through which IL­27 ameliorates inflammatory responses in asthma are not yet fully understood. Thus, the aim of the present study was to examine the effects of IL­27 on asthma using a mouse model and to elucidate the underlying mechanisms. For this purpose, mice received an intranasal administration of IL­27 and the total and differential cell counts, levels of cytokines and type 1 regulatory T (Tr1) cells in the lungs were detected. The protein and mRNA levels of signal transducer and activator of transcription (STAT)1 and STAT3 were analyzed and airway remodeling was assessed. The results indicated that IL­27 did not ameliorate airway inflammation, airway hyperresponsiveness, and airway remolding when administrated therapeutically. Preventatively, the administration of IL­27 decreased the concentrations of Th2 cytokines and increased the number of Tr1 cells. The protein and mRNA levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrate that the prophylactic administration of IL­27 ameliorates asthma by alleviating the lung Th2 inflammatory environment through the restoration of both the STAT1 and STAT3 pathways. IL­27 may thus prove to be useful as a novel agent for the prevention of asthma.

Machine Learning-Based Radiomics for Prediction of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma.

Identifying an epidermal growth factor receptor (EGFR) mutation is important because EGFR tyrosine kinase inhibitors are the first-line treatment of choice for patients with EGFR mutation-positive lung adenocarcinomas (LUAC). This study is aimed at developing and validating a radiomics-based machine learning (ML) approach to identify EGFR mutations in patients with LUAC. We retrospectively collected data from 201 patients with positive EGFR mutation LUAC (140 in the training cohort and 61 in the validation cohort). We extracted 1316 radiomics features from preprocessed CT images and selected 14 radiomics features and 1 clinical feature which were most relevant to mutations through filter method. Subsequently, we built models using 7 ML approaches and established the receiver operating characteristic (ROC) curve to assess the discriminating performance of these models. In terms of predicting EGFR mutation, the model derived from radiomics features and combined models (radiomics features and relevant clinical factors) had an AUC of 0.79 (95% confidence interval (CI): 0.77-0.82), 0.86 (0.87-0.88), respectively. Our study offers a radiomics-based ML model using filter methods to detect the EGFR mutation in patients with LUAC. This convenient and low-cost method may be of help to noninvasively identify patients before obtaining tumor sample for molecule testing.

Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures.

Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.