Kaempferol inhibits colorectal cancer metastasis through circ_0000345 mediated JMJD2C/ß-catenin signalling pathway.

BACKGROUND: Recurrence and metastasis are the main causes of disease deterioration in colorectal cancer (CRC) patients, yet efficient therapeutic strategies are lacking. Natural compounds for efficient antitumour therapeutics are becoming increasingly prominent. Kaempferol, one of the main components of flavonoids in plants, displays a variety of pharmacological activities. Our preliminary experiments suggested that kaempferol could inhibit CRC metastasis and is significantly associated with the ß-catenin signalling pathway. Moreover, we also defined the regulatory roles of JMJD2C in ß-catenin signalling in our previous work. PURPOSE: This study aims to reveal the mechanism by which kaempferol inhibits CRC progression and regulates the JMJD2C/ß-catenin signalling pathway. METHODS: The migratory capabilities of CRC cells after kaempferol intervention were measured by scratch wound healing and transwell assays. Circ_0000345 knockdown CRC stable cell lines were generated by lentivirus infection. The possible mechanism of kaempferol on circ_0000345 was verified by molecular-protein docking and verification program cellular thermal shift assay (CETSA). A dual luciferase reporter gene assay was carried out for the targeting relationship among circ_0000345, miR-205-5p and JMJD2C. Fluorescence in situ hybridization (FISH) was performed to determine the expression of circ_0000345 in tumour tissues. A pulmonary metastatic model of CRC in vitro was built to assess the antimetastatic effect and mechanism of kaempferol in vivo. RESULTS: In vitro, kaempferol inhibits the ability to migrate of CRC cells by reducing the activation of the JMJD2C/ß-catenin signalling pathway. MiR-205-5p is a key bridge for kaempferol to inhibit the expression of JMJD2C. The function of miR-205-5p is impeded by circ_0000345, which shows higher expression levels in human metastatic CRC tissues than nonmetastatic CRC tissues, and its formation is regulated by the RNA-binding proteins HNRNPK and HNRNPL. Mechanistically, kaempferol physically interacts with HNRNPK and HNRNPL to suppress JMJD2C by downregulating the expression of circ_0000345. In vivo, kaempferol suppresses CRC lung metastasis. Kaempferol inhibits the activation of JMJD2C/ß-catenin signalling through reducing the expression of circ_0000345 in the CRC lung metastasis model. CONCLUSION: Circ_0000345 enhances activation of the JMJD2C/ß-catenin signalling pathway through miR-205-5p to promote CRC metastasis. Kaempferol inhibits CRC metastasis through the circ_0000345-mediated JMJD2C/ß-catenin signalling pathway, and this effect is influenced as a direct consequence of the binding of kaempferol with HNRNPK and HNRNPL. This provides promising therapeutic and/or adjuvant agents for advanced CRC and sheds light on the multifaceted role of phytomedicine in cancer.

The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

Therapeutic potential of traditional Chinese medicine on heat stroke.

As global warming progresses, heat waves are becoming increasingly frequent and intense, meanwhile the incidence of heat stroke (HS) has increased sharply during the past decades. HS is typically associated with significant morbidity and mortality, and there is an urgent need for further research to solve this difficult issue. There currently exists difficulties regarding on-site emergency treatment methods and limited in-hospital treatment approaches, and better treatments are required as soon as possible. Theories and therapies from various traditional Chinese medicine (TCM) academic groups have been widely reported. Therefore, an exploration of prevention and protection methods should consider TCM experiences as an alternative. This article primarily reviews TCM herbal therapies and external therapies that have been described in various clinical reports and demonstrated in relevant studies. Herbal therapies, including herbal formulas, Chinese patent medicines (CPMs), single Chinese herbs, and associated extracts or monomers, are summarized based on the shared perspectives of the underlying mechanisms from TCM. In addition, external therapies including acupuncture, bloodletting, cupping, Gua sha and Tui na that have rarely been rarely mentioned and considered in most cases, are introduced and discussed to offer a unique perspective in the search for novel interventions for HS. In summary, TCM may provide abundant potential clinical benefits and research directions in the fight against HS.

The clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease with low body mass index.

Background: This study aimed to analyze the clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease (COPD) with low body mass index (BMI). Methods: In this cross-sectional study, we enrolled patients with stable COPD from the database setup by the Second Xiangya Hospital of Central South University. We classified the patients into three groups based on BMI: low-BMI (<18.5 kg/m2), normal-BMI (≥18.5 and <24.0 kg/m2), and high-BMI (≥24 kg/m2) groups. We defined clinically important deterioration (CID) as a COPD Assessment Test (CAT) score increase of ≥2 and minimum clinically important difference (MCID) as a CAT score decrease of ≥2 during 6 months of follow-up. We recorded the number of exacerbations and mortality during 1 year of follow-up. Results: A total of 910 COPD patients were included with 144 (15.8%) patients in low-BMI, 475 (52.2%) in normal-BMI, and 291 (32.0%) in high-BMI groups. Patients with low BMI had worse pulmonary function, higher symptom scores, and exacerbations in the past year compared with normal- and high-BMI groups (p < 0.05). Logistic regression analysis revealed that age, Global Initiative for Chronic Obstructive Lung Disease grades 3 and 4, and hospitalizations in the past year were independent risk factors for patients with low BMI (p < 0.05). After 1 year of follow-up, patients with low BMI had higher mortality and number of hospitalizations. Patients with low BMI were more likely to attain CID and less likely to attain MCID compared with patients with high BMI (p < 0.05). In addition, patients with low BMI treated with long-acting ß2-agonist (LABA)+long-acting muscarinic antagonist (LAMA) and LABA+LAMA+inhaled corticosteroid (ICS) were more likely to attain MCID than those treated with LABA+ICS and LAMA (p < 0.05). Conclusion: COPD patients with low BMI had worse pulmonary function, higher symptom scores, and higher risk of future hospitalizations and mortality and were less likely to attain MCID and more likely to attain CID. It is worth noting that patients with low BMI treated with LABA+LAMA and LABA+LAMA+ICS were more likely to attain MCID than those treated with LABA+ICS and LAMA.

[Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics].

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

[Effective components and mechanism of Qijiao Shengbai Capsules based on fingerprinting and network pharmacology].

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.

[Rapid flavonoid-focused sub-chemome characterization of Draconis Sanguis using UPLC-Q-TOF-MS in combination with molecular weight imprinting and mass defect filtering].

Draconis Sanguis is a precious Chinese medicinal material for activating blood and resolving stasis, and its effective components are flavonoids. However, the structural diversity of flavonoids in Draconis Sanguis brings great challenges to the in-depth chara-cterization of its chemical composition profiles. To clarify the substance basis of Draconis Sanguis, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used in this study to acquire MS data of Draconis Sanguis. The molecular weight imprinting(MWI) and mass defect filtering(MDF) were developed for rapid screening of flavonoids in Draconis Sanguis. Full-scan MS and MS~2 were recorded within the mass range m/z 100-1 000 in positive ion mode. Accor-ding to previous literature, MWI was employed to hunt for reported flavonoids in Draconis Sanguis, and the mass tolerance range of [M+H]~+ was set as ±10×10~(-3). A five-point MDF screening frame was further constructed to narrow the screening range of flavonoids from Draconis Sanguis. Combined with diagnostic fragment ions(DFI) and neutral loss(NL) as well as mass fragmentation pathways, 70 compounds were preliminarily identified from the extract of Draconis Sanguis, including 5 flavan oxidized congeners, 12 flavans, 1 dihydrochalcones, 49 flavonoids dimers, 1 flavonoids trimer and 2 flavonoid derivatives. This study clarified the chemical composition of flavonoids in Draconis Sanguis. Moreover, it also showed that high-resolution MS combined with data post-processing methods such as MWI and MDF could achieve rapid characterization of the chemical composition in Chinese medicinal materials.

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. PATIENTS AND METHODS: This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. RESULTS: We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. CONCLUSION: Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

The clinical characteristics and outcomes of different inhaled therapies in chronic obstructive pulmonary disease patients with frequent cough.

BACKGROUND: Cough is a common symptom in patients with chronic obstructive pulmonary disease (COPD). Patients with cough may exhibit various clinical characteristics and experience varying outcomes based on inhaled therapies they receive. OBJECTIVES: This study aimed to explore the clinical characteristics and outcomes of various inhaled therapies in COPD patients with frequent cough. METHODS: This was a multicenter, prospective cohort study. Of these patients, the median cough score in COPD assessment test (CAT) was two. Patients were classified into frequent cough group if they scored two or over in the first item of CAT and infrequent cough group otherwise. Patients with frequent cough were then divided into long-acting antimuscarinic (LAMA), long-acting beta2-agonist (LABA)/LAMA, inhaled corticosteroids (ICS)/LABA and ICS/LABA/LAMA groups. Minimum clinically important difference (MCID) (CAT scores decreased ≥2 from baseline) and the improvement of cough (cough score decreased ≥1 from baseline) were collected in the six-month follow-up. Frequent exacerbations (experiencing at least two exacerbations) were collected in the one-year follow-up. RESULTS: Of 906 patients, 581 (64.1%) patients reported frequent cough at the initial visit. Frequent cough was associated with the current smokers and CAT scores (p < 0.05). The MCID showed no significant difference between frequent cough and infrequent cough groups in the follow-up. More patients with frequent cough experienced future frequent exacerbations compared to those with infrequent cough. After receiving inhaled therapies, 62% of patients with frequent cough got the cough improved. More patients with frequent cough treated with LABA/LAMA or ICS/LABA/LAMA attained MCID and fewer experienced exacerbations than those treated with LAMA or ICS/LABA (p < 0.05). The change in cough score showed no difference among various inhaled therapies in patients with frequent cough. CONCLUSION: COPD patients with frequent cough were related to current smokers and higher CAT scores. These patients had a higher incidence of frequent exacerbations than those with infrequent cough. Patients with frequent cough who were treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID and at a lower risk of exacerbation than those treated with LAMA or ICS/LABA.

[Preparation and in vitro release of quercetin nanocrystals self-stabilized Pickering emulsion].

A new quercetin nanocrystals self-stabilized Pickering emulsion(QT-NSSPE) was prepared by high-pressure homogenization combined with probe ultrasonic method. The influences of oil fraction, quercetin(QT) concentration, and pH of water phase on the formation of QT-NSSPE were investigated. On this basis, the QT-NSSPE prepared under optimal conditions was evaluated in terms of microstructure, stability, and in vitro release and the droplet size and drug loading were 15.82 µm and 4.87 mg·mL~(-1), respectively. The shell structure formed by quercetin nanocrystals(QT-NC) on the emulsion droplet surface was observed under a scanning electron microscope(SEM). X-ray diffraction(XRD) showed that the crystallinity of adsorbed QT-NC decreased significantly as compared with the raw QT. There were not significant changes of QT-NSSPE properties after 30 days of storage at room temperature. The in vitro release experiment confirmed that QT-NSSPE has a higher accumulative release rate than the raw QT. All these results indicated that QT-NSSPE has a great stability and a satisfactory in vitro release behavior, which is a promising new oral delivery system for QT.

N-Acetylcysteine alleviates high fat diet-induced hepatic steatosis and liver injury via regulating the intestinal microecology in mice.

N-Acetylcysteine (NAC), a well-accepted antioxidant, has been shown to protect against high fat diet (HFD)-induced obesity-associated non-alcoholic fatty liver disease (NAFLD) in mice. However, the underlying mechanism(s) of the beneficial role of NAC is still not fully understood. Our study aimed to evaluate the protective effect of NAC against NAFLD in terms of gut microbiota homeostasis. Thirty-two C57BL/6 mice were divided into four groups, including chow diet (CHOW), high-fat diet (HFD), CHOW + NAC (2 g L-1 in the drinking water), and HFD + NAC groups, and fed for 12 weeks. NAC supplementation significantly improved HFD-induced obesity, dyslipidemia, and liver dysfunction in mice. NAC also rescued HFD-caused disorder of the gut microbiota. Intriguingly, removing intestinal microorganisms by antibiotics (ABX) obviously abolished NAC supplementation-rescued hepatic steatosis and liver injury, indicating the involvement of the gut microbiota in the beneficial role of NAC. The profiles of 1145 expressed hepatic mRNAs were analyzed by whole transcriptome sequencing. Among those, 5 up-expressed mRNAs induced by a HFD, including Cidea, CD36, Acnat2, Mogat1, and GPAT3, were reversed by NAC treatment, which was further verified by a quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, those 5 mRNAs exhibited a significant (negative or positive) association with bacterial phyla or genera, including phyla Firmicutes and Bacteroidetes and genera norank_f_Erysipelotrichaceae and Lachnoclostridium, by Spearman's correlation analysis. These results suggested that the homeostasis of the gut microbiota plays an important role in NAC-improved NAFLD by affecting the enterohepatic axis.

Effects of Environmental and Spatial Variables on Bacteria in Zhanjiang Mangrove Sediments.

The bottom mud of mangroves contains numerous microbial groups that play an important role in the main ecological functions of the mangrove ecosystem. The diversity and functional and environmental factors related to microbial communities, in terms of the assembly process and in environmental adaptation of the abundance and rare bacterial communities in the mangrove ecosystem, have not been fully explored. We used 16S high-throughput sequencing and operational taxonomic unit analysis to compare the diversity and composition of bacterial communities in different tidal zones in the sediments of the Zhanjiang Gaoqiao Mangrove Nature Reserve, compare the ecological adaptation thresholds and phylogenetic signals of bacterial communities under different environmental gradients, and examine the factors affecting the composition of the bacterial community. The diversity of microbial species and structure and function of the mangrove sediments were affected by the environment, showing the trend: mid tide zone > climax zone > low tide zone. Organic matter content, oxygen content, pH, and total phosphorus were identified as important environmental factors determining the functional diversity of bacterial communities and survival, while pH influences species evolution. The abundant taxa showed a wider response threshold and stronger phylogenetic signals of ecological preference across environmental gradients compared to rare taxa. The abundant bacterial groups have broader environmental adaptability than rare bacterial groups, and different environmental factors affect different communities and functions in the mangrove ecological environment. These results elucidate the mechanism underlying the generation and maintenance of bacterial diversity in response to global environmental changes.

Eriodictyol ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via vitamin D receptor-mediated Nrf2 activation.

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative disease in the contemporary era, and it is still clinically incurable. Eriodictyol, a natural flavonoid compound that is mainly present in citrus fruits and some Chinese herbal medicines, has been reported to exert anti-inflammatory, antioxidant, anticancer and neuroprotective effects. However, few studies have examined the anti-AD effect and molecular mechanism of eriodictyol. METHODS: APP/PS1 mice were treated with eriodictyol and the cognitive function of mice was assessed using behavioral tests. The level of amyloid-ß (Aß) aggregation and hyperphosphorylation of Tau in the mouse brain were detected by preforming a histological analysis and Western blotting. HT-22 cells induced by amyloid-ß peptide (1-42) (Aß1-42) oligomers were treated with eriodictyol, after which cell viability was determined and the production of p-Tau was tested using Western blotting. Then, the characteristics of ferroptosis, including iron aggregation, lipid peroxidation and the expression of glutathione peroxidase type 4 (GPX4), were determined both in vivo and in vitro using Fe straining, Western blotting and qPCR assays. Additionally, the expression level of vitamin D receptor (VDR) and the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway were tested using Western blotting and qPCR assays. Afterward, HT-22 cells with VDR knockout were used to explore the potential mechanisms, and the relationship between VDR and Nrf2 was further assessed by performing a coimmunoprecipitation assay and bioinformatics analysis. RESULTS: Eriodictyol obviously ameliorated cognitive deficits in APP/PS1 mice, and suppressed Aß aggregation and Tau phosphorylation in the brains of APP/PS1 mice. Moreover, eriodictyol inhibited Tau hyperphosphorylation and neurotoxicity in HT-22 cells induced by Aß1-42 oligomer. Furthermore, eriodictyol exerted an antiferroptosis effect both in vivo and in vitro, and its mechanism may be associated with the activation of the Nrf2/HO-1 signaling pathway. Additionally, further experiments explained that the activation of Nrf2/HO-1 signaling pathway by eriodictyol treatment mediated by VDR. CONCLUSIONS: Eriodictyol alleviated memory impairment and AD-like pathological changes by activating the Nrf2/HO-1 signaling pathway through a mechanism mediated by VDR, which provides a new possibility for the treatment of AD.

Real-World Effectiveness of Inhalation Therapy Among Patients With Symptomatic COPD in China: A Multicenter Prospective Study.

Purpose: This real-world study evaluated the effectiveness of different inhalation therapies in patients with symptomatic chronic obstructive pulmonary disease (COPD) in China and also explored the relevant factors that influence the effectiveness of inhalation therapy. Patients and Methods: We conducted a multicenter prospective longitudinal study that was carried out in 12 hospitals in China from December 2016 to June 2021. A face-to-face interview was conducted to collect data. Baseline data were collected at the first visit. Minimum clinically important difference (MCID) was defined as attaining a COPD assessment test (CAT) decrease ≥2. We mainly assessed the MCID and the incidence of exacerbations at the 6 months follow-up. Results: In 695 patients, the mean age was 62.5 ± 8.2 years, with a mean CAT score of 15.1 ± 6.0. Overall, 341 (49.1%) patients attained the MCID of CAT and the incidence of exacerbation during follow-up was 22.3%. Females were significantly more likely to attain MCID than male in COPD patients (adjusted odd ratio (aOR) = 1.93, adjusted 95% confidence interval (a95%CI) = 1.09-3.42, p = 0.024). Patients treated with LABA/LAMA or ICS/LABA/LAMA (ICS, inhaled corticosteroid; LABA, long-acting ß2-agonist; LAMA, long-acting muscarinic antagonist) were more likely to attain MCID than patients treated with LAMA (aOR = 3.97, a95%CI = 2.48-6.35, p < 0.001; aOR = 3.17, a95%CI = 2.09-4.80, p < 0.001, respectively). Patients treated with LABA/LAMA had a higher incidence of severe exacerbation than patients treated with ICS/LABA/LAMA (aOR = 1.95, a95%CI = 1.04-3.66, p = 0.038). Conclusion: The incidence of MCID in symptomatic COPD patients treated with inhalation therapy was nearly 50%. Patients treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID than patients treated with LAMA. Patients treated with LABA/LAMA had a higher incidence of severe exacerbations than with ICS/LABA/LAMA.

Investigation on the surface-active and antimicrobial properties of a natural glycolipid product.

Glycolipids are a group of sugar-containing lipids with versatile functions. In this study, a natural glycolipid product was obtained from soy lecithin, and its emulsifying, oil-gelling, antibacterial and antiviral properties were investigated. A silica-based extraction method on a preparative scale was used to recover the glycolipid product (GLP) from soy lecithin. The GLP consisted of three different glycolipid classes: acylated sterol glucoside (64.16%), sterol glucoside (25.57%) and cerebroside (6.71%). As an emulsifier, the GLP was able to form a stable water-in-oil emulsion. The GLP exhibited a good oil-gelling property, capable of gelling rapeseed oil at a concentration of 6%. For the investigated microorganisms (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus), the GLP did not show any antibacterial effects. The GLP exerted antiviral activity against lentivirus, but not adenovirus. The results of this study help in enriching the knowledge on the properties of naturally occurring glycolipids, which may find potential applications in the food, pharmaceutical and related industries.

[Rapid chemome profiling of Cistanche salsa using DI-MS/MS~(ALL)].

The current study aims to rapidly and comprehensively profile the chemical composition of Cistanche salsa using direct infusion coupled with MS/MS~(ALL)(DI-MS/MS~(ALL)). The C. salsa extract was directly imported into electrospray ionization(ESI) source of quadrupole time-of-flight(Q-TOF) mass spectrometer with an infusion pump at a flow rate of 10 µL·min~(-1). Acquisition program was applied under negative ionization polarity to collect one MS~1 spectrum(m/z 50-1 200), followed by 1 150 MS~2 spectra with precursor isolation window(m/z 1) amongst mass range m/z 50-1 200. After each MS~2 spectrum was matched to its precursor ion, putative identification was conducted through matching mass spectral data with literature and database. A total of 31 components were identified from C. salsa, including 9 phenylethanoid glycosides, 2 iridoids, 4 saccharides, 9 organic acids, and 7 other compounds, similar to those from C. tubulosa and C. deserticola. In conclusion, DI-MS/MS~(ALL), a facile and reliable analytical tool, can be employed for qualitative analysis of chemical constituents in C. salsa. The research offers a promising strategy to achieve rapid chemome profiling of herbal medicine and provides an alternative source of Cistanches Herba.

Drug-containing serum of rhubarb-astragalus capsule inhibits the epithelial-mesenchymal transformation of HK-2 by downregulating TGF-ß1/p38MAPK/Smad2/3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum L; Astragalus membranaceus (Fisch.), is referred to as 'Dahuang, Huangqi' in China. As an important medicinal plant, the rhizome of rhubarb and astragalus is traditionally used in the treatment of kidney diseases associated with renal failure, inflammation and tumors. AIM OF THE STUDY: This study aimed to investigate the effect of a drug-containing serum of rhubarb-astragalus capsules (composed of rhubarb and astragalus) and to elucidate its mechanism in the epithelial-mesenchymal transformation of renal tubular epithelial cells. MATERIALS AND METHODS: Epithelial-mesenchymal transformation (EMT) of HK-2 cells was induced by TGF-ß1, and rhubarb-astragalus and losartan drug-containing serum from rats, as well as SB203580 (a specific inhibitor of p38 MAPK), were used. High-performance liquid chromatography analysis was performed to determine the main components of the drug-containing serum of rhubarb-astragalus from rats. Western blotting and immunofluorescence analysis were used to determine the levels of protein expression, and real-time quantitative PCR analysis was used to detect the levels of gene expression. RESULTS: The drug-containing serum of rhubarb-astragalus contained emodin (0.36 µg/ml) and danthraquinone (0.96 µg/ml). Rhubarb-astragalus significantly decreased the protein expression levels of α-SMA, FN, vimentin and N-cadherin in HK-2 cells that were increased by TGF-ß1, while it significantly increased the E-cadherin protein expression level that was decreased by TGF-ß1. Rhubarb-astragalus also significantly decreased the protein expression levels of TGF-ß1 and p38 MAPK and the mRNA expression levels of α-SMA, vimentin, TGF-ß1, p38 MAPK, Smad2 and Smad3 in HK-2 cells that were increased by TGF-ß1. It is worth noting that SB203580 (a p38 MAPK inhibitor) had similar effects as rhubarb-astragalus in this study. CONCLUSION: The drug-containing serum of rhubarb-astragalus can inhibit EMT in HK-2 cells by downregulating the TGF-ß1/p38 MAPK/Smad2/3 pathway.

Ultrasound-guided implantation of radioactive 125I seed in radioiodine refractory differentiated thyroid carcinoma.

BACKGROUND: Treatment for radioiodine refractory differentiated thyroid carcinoma (RR-DTC) is challenging. The purpose of this study was to assess the efficacy and safety of ultrasound-guided implantation of radioactive 125I-seed in radioiodine refractory differentiated thyroid carcinoma. METHODS: Thirty-six cervical metastatic lymph nodes (CMLNs) diagnosed with RR-DTC from 18 patients were enrolled in this retrospective study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before implantation. Follow-up comprised US, CEUS, thyroglobulin (Tg) level and routine hematology at 1-3, 6, 9 and 12 months and every 6 months thereafter. The volumes of the nodules were compared before implantation and at each follow-up point. The volume reduction rate (VRR) of nodules was also recorded. RESULTS: The median volume of the nodules was 523 mm3 (148, 2010mm3) initially, which decreased significantly to 53mm3 (0, 286mm3) (P < 0.01) at the follow-up point of 24 months with a median VRR as 95% (86,100%). During the follow-up period (the range was 24-50 months), 25 (69%) nodules had VRR greater than 90%, of which 12 (33%) nodules had VVR ≈ 100% with unclear structures and only 125I seed images were visible in the US. At the last follow-up visit, the serum Tg level decreased from 57.0 (8.6, 114.8) ng/ml to 4.9 (0.7, 50.3) ng/ml, (P < 0.01). CONCLUSION: US-guided 125I seed implantation is safety and efficacy in treating RR- DTC. It could be an effective supplement for the comprehensive treatment of thyroid cancer.

Exertional rhabdomyolysis in newly enrolled cadets of a military academy.

INTRODUCTION/AIMS: Exertional rhabdomyolysis (ER) often occurs during prolonged intense exercise in hot environments, posing a threat to the health of military personnel. In this study we aimed to investigate possible risk factors for ER and provide further empirical data for prevention and clinical treatment strategies. METHODS: A retrospective investigation of 116 concurrent ER cases was conducted. Conditional logistic regression analyses were performed to assess the association between each potential risk (or protective) factor and ER. The clinical characteristics of the 71 hospitalized patients were analyzed descriptively. RESULTS: After screening, the following variables significantly increased the risk of ER: shorter length of service (recruits; odds ratios [OR], 7.49; 95% confidence interval [CI], 2.58-21.75); higher body mass index (BMI; OR, 1.14, 95% CI, 1.03-1.26); lack of physical exercise in the last half year (less than once per month; OR, 3.20; 95% CI, 1.08-9.44); and previous heat injury (OR, 2.94; 95% CI, 1.26-6.89). Frequent fruit consumption (OR, 0.57; 95% CI, 0.33-0.99), active hydration habit (OR, 0.37; 95% CI, 0.20-0.67), water replenishment of more than 2 L on the training day (OR, 0.15; 95% CI, 0.05-0.45), and water replenishment of at least 500 mL within 1 hour before training (OR, 0.33; 95% CI, 0.12-0.88) significantly decreased the risk of ER. Of the 71 hospitalized patients, 41 (57.7%) were diagnosed with hypokalemia on admission. DISCUSSION: In military training, emphasis should be placed on incremental adaptation training before more intense training, and close attention should be given to overweight and previously sedentary recruits. Fluid replenishment before exercise, increased fruit intake, and proper potassium supplementation may help prevent ER.

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes.

OBJECTIVE: It is aimed at investigating the mechanism of palmitic acid (PA) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (nNOS) protein. METHODS: The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin II-induced hypertensive model rats. The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of Kent Coda, USA. The Ionoptix single-cell contraction detection system was used to detect myocardial cells. ATP level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by Western blot. RESULTS: Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; PA increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and PA increased the intracellular ATP level of rats in the sham group but not in the hypertension group. In the hypertension group, the expression of nNOS in the cardiomyocytes was significantly increased, and specific nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was found to restore the positive inotropic effect of PA in the myocardium of the hypertension group. PA was supplemented after using CPT-1 inhibitor etomoxir (ETO); it was found that ETO inhibited the positive inotropic effect of PA on left ventricular cardiomyocytes in the sham group, and PA was supplemented after using SMTC and ETO, it was found that SMTC + ETO could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in myocardium of hypertensive rats. CONCLUSION: PA could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, PA enhanced the contractility of cardiomyocytes by increasing ATP level in them, and the inhibitory effect of PA on myocardial contractility in hypertensive rats may be related to the increased nNOS and CPT-1 in cardiomyocytes.