Identifying chemical markers in wine-processed Salvia miltiorrhiza using ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry.

To find the chemical markers of wine-processed Salvia miltiorrhiza (WSM), 76 constituents, including diterpenoid quinones and phenolic acids in Salvia miltiorrhiza (SM) and WSM, were profiled using ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS/MS) in positive- and the negative-ion modes. Thirty compounds were screened out as candidate differential components using chemometrics analysis, and the concentration of most compounds increased after processing with wine. Seven compounds, namely tanshinone IIA, magnesium lithospermate B, salvianolic acid G, cryptotanshinone, isocryptotanshinone, salvianolic acid B, and rosmarinic acid, were selected as chemical markers of WSM using variable importance of the project. This study revealed the chemical markers of WSM and confirmed that WSM can improve the extraction and solubility effect of chemical constituents.

Corn silk polysaccharides attenuate diabetic nephropathy through restoration of the gut microbial ecosystem and metabolic homeostasis.

Introduction: The pathogenesis of diabetic nephropathy (DN) is complex, inflammation is the central link among the inducing factors in the existing research, and the gutkidney axis could scientifically explain the reasons for the accumulation of chronic low-grade inflammation. As both a medicine and food, corn silk contains abundant polysaccharides. Historical studies and modern research have both confirmed its intervention effect on diabetes and DN, but the mechanism of action is unclear. Methods: In this study, a DN rat model was generated, and the therapeutic effect of corn silk polysaccharides (CSPs) was evaluated based on behavioral, histopathological and biochemical indicators. We attempted to fully understand the interactions between CSPs, the gut microbiota and the host at the systemic level from a gut microbiota metabolomics perspective to fundamentally elucidate the mechanisms of action that can be used to intervene in DN. Results: Research has found that the metabolic pathways with a strong correlation with CSPs were initially identified as glycerophosphate, fatty acid, bile acid, tyrosine, tryptophan and phenylalanine metabolism and involved Firmicutes, Bacteroides, Lachnospiraceae-NK4A136- group and Dubosiella, suggesting that the effect of CSPs on improving DN is related to changes in metabolite profiles and gut microbiota characteristics. Discussion: CSPs could be harnessed to treat the abnormal metabolism of endogenous substances such as bile acids and uremic toxins caused by changes in gut microbiota, thus alleviating kidney damage caused by inflammation. In view of its natural abundance, corn silk is safe and nontoxic and can be used for the prevention and treatment of diabetes and DN.

Experience of Autologous Stem Cell Transplant in Multiple Myeloma: The Patient and Caregiver Perspective.

A qualitative study of the experiences of patients who received autologous stem cell transplant (ASCT) for the treatment of multiple myeloma (MM) was conducted to better understand their MM disease journey, including first symptoms, diagnosis, ASCT, and recovery. Sixteen participants, including 12 patients with MM and 4 caregivers of patients with MM, were interviewed in focus group meetings. Pain, weakness, and bone pain were common first symptoms among patients. The MM diagnosis was often made by a hematologist or oncologist. Patients were referred to a specialized oncologist after diagnosis, who was the primary driver in making ASCT treatment decisions. Eight patients received their ASCT in the inpatient setting, with some having lengthy hospital stays; 4 received their ASCT in an outpatient setting with 3 eventually being hospitalized. The focus groups identified that patients and caregivers perceived various unmet needs and impacts on quality of life throughout their transplant journey. Educational resources and innovative therapies are needed to reduce the disease burden of MM and enhance the quality of life for both patients and their caregivers.

Study on molecular mechanism of volatiles variation during Bupleurum scorzonerifolium root development based on metabolome and transcriptome analysis.

Bupleurum scorzonerifolium Willd. is a medicinal herb. Its root has a high content of volatile oil (BSVO), which shows a variety of biological activities. Currently, BSVO in the injectable form is used for treating fever in humans and livestock. The yield and quality of volatile oils depends on the developmental stages of plants. However, the changes in BSVO yield and quality during root development in Bupleurum scorzonerifolium and the underlying molecular regulatory mechanisms remain unclear. This knowledge gap is limiting the improvement in the quality of BSVO. In the present study, B. scorzonerifolium root was collected at germinative, vegetative, florescence, fruiting and defoliating stages. The yield of BSVO, metabolic profile of volatile components and transcriptome of root samples at various developmental stages were comprehensively determined and compared. BSVO continuously accumulated from the germinative to fruiting stages, and its level slightly decreased from the fruiting to defoliating stages. A total of 82 volatile components were detected from B. scorzonerifolium root, of which 22 volatiles were identified as differentially accumulated metabolites (DAMs) during the root development. Of these volatiles, fatty acids and their derivatives accounted for the largest proportion. The contents of most major volatiles were highest at the fruiting stage. A large number of differentially expressed genes (DEGs) were detected during B. scorzonerifolium root development, of which 65 DEGs encoded various enzymes and transcription factors regulating the biosynthesis of fatty acids and their derivatives. In further analysis, 42 DEGs were identified to be significantly correlated with DAMs, and these DEGs may be the key genes for the biosynthesis of volatiles. To the best of our knowledge, this is the first study to comprehensively report the changes in the composition and content of volatiles and underlying mechanism during B. scorzonerifolium root development. This study provided important reference for future studies to determine the harvest time of B. scorzonerifolium roots and improve the quality of BSVO.

Two new terpenoids with anti-inflammatory activity from the fruits of Arenga pinnata (Wurmb) Merr.

Two new terpenoids (1 and 2), arenterpenoid D (1) and pinnasesquiterpene A (2), along with 16 phenylpropanoids (3-18) and 8 known terpenoids (19-26) were isolated from 70% EtOH extract of the Arenga pinnata (Wurmb) Merr. fruits. Their structures were elucidated by spectroscopic methods including HR-ESI-MS, 1D, and 2D NMR. The absolute configuration of arenterpenoid D (1) was defined by X-ray crystallographic analysis. Furthermore, we evaluated the anti-inflammatory activity of all compounds, and outcomes showed that 2 and 21 exposed moderate suppressive effects against NO generation in lipopolysaccharide-stimulated RAW 264.7 cells.

[Therapeutic material basis of Daqinglong Decoction: based on serum pharmacochemistry and network pharmacology].

Based on the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology, the components of Daqinglong Decoction absorbed in serum were analyzed and identified, and the therapeutic material basis of the prescription was revealed via network pharmacology. UPLC conditions are as follows: Waters Acquity UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), mobile phase of 0.1% formic acid aqueous solution(A)-0.1% formic acid in acetonitrile(B), gradient elution. Peakview 2.0 and MetabolitePilot 1.5 were employed for the comparison of Daqinglong Decoction, blank serum, and serum after the administration of the decoction, and the components of Daqinglong Decoction absorbed in serum were analyzed based on MS/MS profiles in related database and literature. The targets of the components absorbed in serum were retrieved from SwissTargetPrediction, DrugBank, and Batman-TCM. With the search terms of common cold, influenza, flu, bronchitis, bronchiolitis, asthma, allergic rhinitis, rhinallergosis, allergic coryza, rheumatic arthritis, and nephritis, the related disease targets were screened out. Then the absorbed component-potential target gene network and absorbed component target-disease target network were constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the core targets. iGEMDOCK was employed for molecular docking of the absorbed components and core targets. In the serum after the administration of the decoction, 28 components were preliminarily identified, with 21 prototypes and 7 metabolites. Among them, 5 core components of ephedrine, demethylephedrine, glycyrrhetinic acid, p-hydroxybenzoic acid, and 2-methoxybenzoic acid were screened out, and 9 core targets, such as JUN, tumor protein 53(TP53), and protein kinase B(AKT1), were identified. Molecular docking showed high binding affinity of core components and core targets. Therefore, Daqinglong Decoction may exert therapeutic effect by regulating mitogen-activated protein kinase(MAPK), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) signaling pathways and further improving and regulating inflammatory response and other physiological and pathological processes. This study clarifies the components of Daqinglong Decoction absorbed in serum and explores the therapeutic material basis of the prescription, which provides a reference for further elucidating the mechanism of Daqinglong Decoction and its clinical application.

Study of Saponin Components after Biotransformation of Dioscorea nipponica by Endophytic Fungi C39.

This study conducted the solid fermentation process of Dioscorea nipponica using endophytic fungi C39 to determine the changes in the diosgenin concentration. The results revealed that endophytic fungi C39 could effectively biotransform the saponin components in D. nipponica. Moreover, the maximum increase in the diosgenin concentration reached 62.67% in 15 days of solid fermentation. MTT assay results demonstrated that the inhibitory effects of the fermentation drugs on four types of cancer cells (liver cancer cells (HepG2), stomach cancer cells (BGC823), cervical cancer cells (HeLa), and lung cancer cells (A549)) were better than those of the crude drugs obtained from D. nipponica. The chemical composition of the samples obtained before and after the biotransformation of D. nipponica was analyzed by UPLC-Q-TOF-MS. A total of 32 compounds were identified, 21 of which have been reported in Dioscorea saponins and the ChemSpider database and 11 compounds were identified for the first time in D. nipponica. The biotransformation process was inferred based on the variation trend of saponins, which included transformation pathways pertaining to glycolytic metabolism, ring closure reaction, dehydrogenation, and carbonylation. The cumulative findings provide the basis for the rapid qualitative analysis of the saponin components of D. nipponica before and after biotransformation. The 11 metabolites obtained from biotransformation are potential active ingredients obtained from D. nipponica, which can be used to further identify pharmacodynamically active substances.

Exploring the mechanism of Qinbaiqingfei-concentrate pills in the treatment of Mycoplasma pneumoniae pneumonia from the perspective of intestinal microbiota and mucosal immunity.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine categorizes Mycoplasma pneumoniae pneumonia as "lung heat", and treatment with heat clear and detoxify. Traditional Chinese medicine believes that the lungs and intestines come from the same source, and the intestine is related to pneumonia. This is the same as the gut-lung axis theory. Qinbaiqingfei concentrate pills (QBs) were modified based on Cough San in the ancient medical book Medical Awareness. It clears lung heat, moisturizes the lungs and dredges collaterals, and has a good ability to treat Mycoplasma pneumoniae. AIM OF THE STUDY: A rat model of Mycoplasma pneumoniae was established. From the aspect of intestinal flora and mucosal immunity, the potential mechanism of the QBs was researched. MATERIALS AND METHODS: First, the content of Mycoplasma pneumoniae in lung tissue and the levels of the inflammatory factors IL-4, IL-10, TNF-α and INF-γ were detected. To determine the expression of NF-kB related proteins in lung tissue, which can understand the ability in treating disease. Next, metagenomic sequencing was performed to detect changes in short-chain fatty acids, proving the ability of the drug to regulate intestinal microecology. Finally, HDAC, LPS, SIgA, etc. were detected to facilitate the correlation of the overall experimental indicators. RESULTS: QBs reduces the levels of IL-4, IL-10, TNF-α and INF-γ in the serum by inhibiting the expression of MyD88, IKKα, IκBα, and NF-κB p65 in lung tissue. In addition, QBs restores the ratio of gram-negative bacteria to gram-positive bacteria in the intestine, restores the secretion of acetic acid, propionic acid, butyric acid, isobutyric acid and isovaleric acid, and promotes the secretion of NF-κB p65 and SIgA by HDAC1/3. The result is that the lung tissue is repaired and the proliferation of Mycoplasma pneumoniae is inhibited. CONCLUSIONS: From the "gut-lung axis", a new research perspective was discovered. QBs intervened in the intestines and lungs to treat Mycoplasma pneumoniae.

Integrated Metabolomics and Network Pharmacology Analysis Immunomodulatory Mechanisms of Qifenggubiao Granules.

Background: Qifenggubiao granules (QFGBG) is a new Chinese medicine independently developed by Heilongjiang Academy of Traditional Chinese Medicine, which combines the essence of Yupingfeng powder and Shengmai yin (invention patent number: CN1325098C, approval number: Sinopharm Zhunzi B20020410), and has been included in the 2020 edition of Chinese Pharmacopoeia. It has remarkable pharmacodynamic results and conclusive clinical effects in the treatment of allergic rhinitis, chronic cough and other diseases. Previous pharmacological studies have shown that it has immunomodulatory effect, but its immunomodulatory mechanism is still unclear. Methods: In this study, cyclophosphamide (CTX) was used to establish the immune hypofunction model in mice, and the weight change, index of immune organs in spleen and thymus, pathological sections of immune organs and inflammatory factors were used to evaluate the model. Based on the metabolic biomarkers obtained by metabonomics technology, the potential targets of Qifeng Gubiao Granule immunomodulation were obtained by integrating the targets of blood components, metabolites and diseases through network pharmacology. Meanwhile, GO enrichment analysis and KEGG pathway analysis were carried out on the potential targets. Results: QFGBG can increase body weight and organ index, and recover immune organ damage caused by CP. Metabonomics identified 13 metabolites with significant changes, among which the level of phospholipid (PC) metabolites decreased significantly in the model group. Sphingosine -1- phosphate, 1- palmitoyl phosphatidylcholine [LysoPC (16:0/0:0)] and other metabolites were significantly increased in the model group, and 98 targets of Qifeng's external immune regulation were obtained by intersecting 629 component targets, 202 metabolite targets and 1916 disease targets. KEGG pathway analysis obtained 233 related metabolic pathways, and the top 20 metabolic pathways mainly involved IL-17 signaling pathway, TNF signaling pathway, Sphingolipid signaling pathway, and so on. Conclusion: QFGBG may act on AKT1, IL6, MAPK3, PTGS2, CASP3, MAPK1, ESR1, PPARG, HSP90AA1, PPARA and other targets, acting through Sphingolipid signaling pathway and signaling pathway. Combined with pharmacodynamic evaluation, the immunomodulatory effect of QFGBG was confirmed, and the immunomodulatory mechanism of QFGBG with multiple targets and multiple pathways was preliminarily clarified.

Sociodemographic and Clinical Characteristics Associated With Worst Pain Intensity Among Cancer Patients.

AIMS: Patients with cancer have pain due to their cancer, the cancer treatment and other causes, and the pain intensity varies considerably between individuals. Additional research is needed to understand the factors associated with worst pain intensity. Our study aim was to determine the association between worst pain intensity and sociodemographics and cancerspecific factors among patients with cancer. DESIGN: A total of 1,280 patients with cancer recruited from multiple cancer centers over 25 years in the United States were asked to complete a questionnaire that collected respondents' demographic, chronic pain, and cancer-specific information. SETTINGS: Worst, least, and current pain intensities were captured using a modified McGill Pain Questionnaire (pain intensity measured on 0-10 scale). A generalized linear regression analysis was utilized to assess the associations between significant bivariate predictors and worst pain intensity scores.Our study sample was non-Hispanic White (64.5%), non-Hispanic Black (28.3%), and Hispanic (7.2%). On average, participants were 59.4 (standard deviation = 14.4) years old. The average worst pain intensity score was 6.6 (standard deviation = 2.50). After controlling for selected covariates, being Hispanic (ß = 0.6859), previous toothache pain (ß = 0.0960), headache pain (ß = 0.0549), and stomachache pain (ß = 0.0577) were positively associated with worse cancer pain. Notably, year of enrollment was not statistically associated with pain. CONCLUSIONS: Our study sample was non-Hispanic White (64.5%), non-Hispanic Black (28.3%), and Hispanic (7.2%). On average, participants were 59.4 (standard deviation = 14.4) years old. The average worst pain intensity score was 6.6 (standard deviation = 2.50). After controlling for selected covariates, being Hispanic (ß = 0.6859), previous toothache pain (ß = 0.0960), headache pain (ß = 0.0549), and stomachache pain (ß = 0.0577) were positively associated with worse cancer pain. Notably, year of enrollment was not statistically associated with pain. Findings identified being Hispanic and having previous severe toothache, stomachache, and headache pain as significant predictors of worst pain intensity among patients with cancer. After controlling for selected covariates, we did not note statistical differences in worst pain during a 25-year period. Therefore,studies focused on improving the management of pain among patients with cancer should target interventions for those with Hispanic heritage and those with past history of severe common pain.

Economic analysis of a pediatric neurosurgery telemedicine clinic.

OBJECTIVE: The authors' objective was to compare the actual cost of a regional pediatric neurosurgery telemedicine clinic (PNTMC) with the estimated cost of a traditional physician-staffed outreach clinic. METHODS: The authors' PNTMC was a partnership between the University of Florida College of Medicine-Jacksonville and Georgia Children's Medical Services to service the population of Georgia's Southeast Health District. Neurosurgeons based in Jacksonville conducted telemedicine visits with patients located at a remote site in Georgia with the assistance of nursing personnel from Children's Medical Services. The authors determined the actual annual per-patient costs at the Jacksonville and Georgia sites for fiscal years 2018 (FY18) and 2019 (FY19) and estimated the cost of providing traditional physician-staffed outreach clinics. RESULTS: During FY18 and FY19, the neurosurgery team conducted an average of 24.5 telemedicine patient encounters per year at a cost of $369 per patient visit. The per-patient cost was 32.5% less than the estimated per-patient cost of $547 at a traditional outreach clinic. CONCLUSIONS: The authors provided neurosurgical telehealth visits to appropriate patients, with a substantial cost savings per patient visit compared with traditional physician-staffed outreach clinics.

Projections of the economic burden of care for individuals with dementia in mainland China from 2010 to 2050.

BACKGROUND: China has stepped into an era of aging society, where the impending considerable economic burden attributed to high prevalence of dementia in the elderly appears to be one of the most important health and social issues to deal with for the country. However, population-based quantification and projections for the economic burden of dementia in China are lacking for further health action and policy making. OBJECTIVE: To estimate and predict the costs of managing dementia in the elderly population aged 60 and above from 2010 to 2050 in China. METHODS: Data were collected from a six-province study (n = 7072) and other multiple sources for calculation of the economic burden of dementia. With the convincing data from published studies, we quantified and projected the costs attributed to dementia in China from 2010 to 2050. RESULTS: The national cost of dementia in 2010 was estimated to be US$22.8 billion by the opportunity cost method and US$26.4 billion by the proxy method. In 2050, the costs would increase to US$372.3 billion by the opportunity cost method and US$430.6 billion by the proxy method, consuming 0.53% and 0.61% of China's total GDP, respectively. A series of sensitivity analyses showed that the changes in the proportions of informal caregiving led to the most robust changes in the total burden of care for dementia in China. CONCLUSION: Dementia represents an enormous burden on China's population health and economy. Due to the changes in policies and population structure, policymakers should give priority to dementia care.

Procedural complications associated with invasive diagnostic procedures after lung cancer screening with low-dose computed tomography.

INTRODUCTION: Although the National Lung Screening Trial (NLST) has proven low-dose computed tomography (LDCT) is effective for lung cancer screening, little is known about complication rates from invasive diagnostic procedures (IDPs) after LDCT in real-world settings. In this study, we used the real-world data from a large clinical research network to estimate the complication rates associated with IDPs after LDCT. METHODS: Using 2014-2021 electronic health records and claims data from the OneFlorida clinical research network, we identified case individuals who underwent an IDP (i.e., cytology or needle biopsy, bronchoscopy, thoracic surgery, and other surgery) within 12 months of their first LDCT. We matched each case with one control individual who underwent an LDCT but without any IDPs. We calculated 3-month incremental complication rates as the difference in the complication rate between the case and control groups by IDP and complication severity. RESULTS: Among 7,041 individuals who underwent an LDCT, 301 (4.3%) subsequently had an IDP within 12 months following the LDCT. The overall 3-month incremental complication rate was 16.6% (95% confidence interval [CI]: 9.9% - 23.1%), higher than that reported in the NLST (9.4%). The overall incremental complication rate was 5.6% (95% CI: 1.9% - 9.6%) for major, 8.6% (95% CI: 3.1% - 14.1%) for intermediate, and 13.2% (95% CI: 8.1% - 18.5%) for minor complications. CONCLUSIONS: It is important to ensure adherence to clinical guidelines for nodule management and downstream work-up to minimize potential harms from screening.

Pathways of Teach-Back Communication to Health Outcomes Among Individuals With Diabetes: A Pathway Modeling.

Teach-back method can help promote interactive communication between patients and providers. However, the mechanism of how teach-back operates in routine care is uninvestigated. Using pathway analysis, we explored the potential pathways of patient teach-back to health outcomes among individuals with diabetes. Study sample included 2901 US adults with diabetes ascertained from the 2011 to 2016 Longitudinal Medical Expenditure Panel Survey. Our pathway model analysis showed that patient teach-back was associated with better interaction with providers, shared decision-making, and receiving lifestyle advice. Teach-back had a direct negative effect on condition-specific hospitalization and indirect negative effects through lifestyle advice and diabetic complication. Teach-back method may promote active interactions between patients and providers by creating an opportunity to be more engaged in shared decision-making and receive additional health advice from providers. These improvements seem to be associated with a reduction in risks for complications and related hospitalization.

Studies on biotransformation mechanism of Fusarium sp. C39 to enhance saponin content of Paridis Rhizoma.

Paridis Rhizoma is a natural medicine with strong anti-tumor and anti-inflammatory activities. Our previous research have found that Fusarium sp. C39, an endophytic fungus isolated from Dioscorea nipponica which contains the similar chemical components, significantly increased the steroidal saponins content of Paridis Rhizoma by fermentation. In this study, the inhibitory effects of fermentated Paridis Rhizoma extract (PRE) on liver cancer cells (Hepal-6), cervical cancer cells (Hela), and lung cancer cells (A549) were determined to be stronger than that of the unfermented extract. For discovering the fermentation mechanism of PRE with Fusarium sp. C39, 36 components with obviously quantitative variations were screened out by UPLC-Q/TOF-MS and 53 key genes involved in the metabolic pathways of steroidal saponins were identified by transcriptome. On the basis of comprehensively analyzing information from the metabonomics and transcriptome, it can be speculated that the increase of spirostanol saponins and nuatigenin-type saponins enhanced the inhibitory effect of fermented PRE on cancer cell proliferation. Under the action of glycosidase, glycosyltransferase, oxidoreductases, and genes involved in sterol synthesis, strain C39 achieved the synthesis of diosgenin and the alteration of configurations, sugar chain and substituent of steroidal saponins. The research suggested a microbial transformation approach to increase the resource utilization and activity of Paris polyphylla.

The antifibrotic effect of pheretima protein is mediated by the TGF-ß1/Smad2/3 pathway and attenuates inflammation in bleomycin-induced idiopathic pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pheretima is a traditional Chinese medicine that could treat various lung diseases such as asthma, pneumonia, and lung cancer effectively; however, limited studies on the use of Pheretima protein in the treatment of lung diseases have been conducted to date. AIM OF THE STUDY: The aim of this study was to explain the antipulmonary fibrosis mechanism of the Pheretima protein and elucidate its possible cell signaling pathways. MATERIAL AND METHODS: Fresh pheretima was freeze-dried to obtain the Pheretima protein. Divide C57BL/6 mice into control and bleomycin (BLM)-induced models, pirfenidone, and Pheretima protein-treatment groups. Three weeks later, they were treated with H&E and Masson's trichrome staining to assess lung injury and fibrosis. Pulmonary fibrosis was assessed using immunohistochemistry (IHC), realtime-PCR (RT-PCR), and western blotting. Inflammation was assessed using the alveolar lavage fluid. RESULTS: Pheretima protein inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition and reduced inflammation. It also reduced the levels of Smad2/3, pSmad2/3, and transforming growth factor-beta 1 (TGF-ß1). Thus, our results indicate that Pheretima protein can alleviate BLM-induced pulmonary fibrosis in a mouse model. CONCLUSION: Pheretima protein inhibits ECM, EMT, and antiinflammatory markers, which in turn ameliorates BLM-induced pulmonary fibrosis. Preliminary mechanistic studies indicated that Pheretima protein can exert its biological activity by downregulating the TGF-ß1/Smad2/3 pathway.

Integrated molecular biology and metabonomics approach to understand the mechanism underlying reduction of insulin resistance by corn silk decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Corn silk is composed of the style and stigma of Zea mays L. Its medical value was first reported in "Southern Yunnan Materia Medica" in the Ming Dynasty. It was considered to be a heat-clearing and diuretic drug. In "Zhejiang Folk Herbal Medicine," the following has been reported: "Corn silk needs one liang. Decoction in water can cure diabetes." Recent studies have shown that corn silk can lower blood sugar levels; however, to date, corn silk has undergone simple pharmacodynamic evaluations, with both its degree and mechanism of action remaining unclear. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of corn silk, with respect to having antioxidative ability, reducing insulin resistance, and having a hypoglycemic effect. MATERIALS AND METHODS: In this study, a type 2 diabetes mellitus (T2DM) rat model was established via a high sugar and high fat diet combined with streptozotocin (35 mg/kg) administration. Wistar rats were administered corn silk decoction and metformin via gavage for four weeks, and the fasting blood glucose (FBG) and body weight were measured every two weeks. After the experiment, the insulin level, insulin index, and glycogen content were determined. Hematoxylin-eosin staining was used to observe the morphological changes of the skeletal muscle tissue in rats. The levels of malondialdehyde and superoxide dismutase in the serum and skeletal muscle were detected, and the mRNA content and protein levels of key proteins in the JNK-IRS-GLUT4 signaling pathway were determined using real-time quantitative polymerase chain reaction and western blotting. Then, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, combined with multiple statistical analyses, was used to identify potential biomarkers in the serum of T2DM rats, for determining the key metabolic pathways responsible for the action of corn silk. RESULTS: The results showed that corn silk could reduce FBG, insulin level, and glycogen content in T2DM rats; reduce the level of oxidative stress in serum and skeletal muscle; restore the pathological structure of skeletal muscle; inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate (IRS) in skeletal muscle; and upregulate the expression of glucose transporter type 4 (GLUT4) for transport of glucose and to reduce insulin resistance. Moreover, metabonomic analysis elucidated that corn silk could significantly affect 26 biomarkers (such as pentosidine, palmitic acid, lysoPC, and p-Cresol sulfate) and metabolic pathways (such as phenylalanine metabolism, phospholipid metabolism, bile acid metabolism, and biosynthesis of unsaturated fatty acids). CONCLUSION: The interaction between endogenous metabolites and proteins in signaling pathways was analyzed using metabonomics and molecular biology methods. Corn silk inhibited JNK-IRS-GLUT4 signal transduction in skeletal muscle via antioxidative effects, by increasing the sensitivity of peripheral tissue to insulin, by reducing insulin resistance, and through hypoglycemic effects.

Health Care Utilization and Costs Associated With Systemic First-Line Metastatic Melanoma Therapies in the United States.

PURPOSE: US Food and Drug Administration approvals of immune checkpoint inhibitors and targeted therapies revolutionized the treatment of metastatic melanoma. Our aim was to assess health care resource utilization and costs for patients with metastatic melanoma treated with systemic therapies in first line between January 2012 and December 2017. METHODS: We conducted a retrospective cohort study of patients with metastatic melanoma using MarketScan data. We included patients diagnosed with melanoma and secondary malignant neoplasm who used pembrolizumab, nivolumab, ipilimumab, ipilimumab plus nivolumab, BRAF-inhibitor (BRAF-i) plus MEK inhibitor (MEK-i), BRAF-i or MEK-i monotherapy, or chemotherapy in first line. We compared health care utilization and costs per patient per month (PPPM) using two-part and generalized linear models. RESULTS: We identified 1,870 patients, including 185 pembrolizumab, 103 nivolumab, 689 ipilimumab, 185 nivolumab plus ipilimumab, 214 BRAF-i plus MEK-i, 240 BRAF-i or MEK-i monotherapy, and 254 chemotherapy users. Highest PPPM rates of hospitalizations, emergency room visits, and outpatient visits were observed in patients with ipilimumab plus nivolumab therapy (adjusted difference v pembrolizumab [aDiff], 0.18, 0.12, and 0.88, respectively; all P < .001). Ipilimumab monotherapy users (aDiff, 0.07 and 0.93; all P < .001) and chemotherapy users (aDiff, 0.10 and 2.63; all P < .001) showed higher PPPM rates of hospitalizations and outpatient visits compared with pembrolizumab users, respectively. Utilization rates in nivolumab, BRAF-i plus MEK-i, and BRAF-i or MEK-i groups were similar to the pembrolizumab group. Highest PPPM total costs and drug-related costs were observed in the ipilimumab group ($80,139 US dollars [USD] and $70,051 USD; all P < .001), followed by the ipilimumab plus nivolumab ($71,689 USD and $56,217 USD; all P < .001) and the BRAF-i plus MEK-i group ($31,184 USD and $19,648 USD; all P < .001). PPPM costs in the nivolumab group were similar to the pembrolizumab group. CONCLUSION: Significant differences in health care resource utilization and costs were found across first-line metastatic melanoma regimens. Utilization rates were highest in patients using ipilimumab-containing therapies. High drug costs constituted a major fraction of total PPPM health care costs.

A Study Based on Metabolomics, Network Pharmacology, and Experimental Verification to Explore the Mechanism of Qinbaiqingfei Concentrated Pills in the treatment of Mycoplasma Pneumonia.

Qinbaiqingfei concentrated pills (QB) are a commonly used medicine for the treatment of mycoplasma pneumonia in China, and the mechanism of action of QB needs to be studied further. Therefore, we use a combination of metabolomics and network pharmacology to clarify the mechanism of QB. Nontarget metabolomics studies were performed on rat serum, urine, and lung tissues, and 56 therapeutic biomarkers were found. Subsequently, the components of QB absorbed into the blood and lung tissues were clarified, and based on this finding, the core target of network pharmacology was predicted. The enrichment analysis of biomarkers-genes finally confirmed their close relationship with the NF-κB signaling pathway. By western blotting expression of the proteins in the lung tissue-related signaling pathways, it is finally confirmed that QB inhibits the NF-κB signaling pathway through SIRT1, IL-10 and MMP9, CTNNB1, EGFR, and other targets. It plays a role in regulating immunity, regulating metabolism, and treating diseases.

Comparing the downstream costs and healthcare utilization associated with the use of low-dose computed tomography (LDCT) in lung cancer screening in patients with and without alzheimer's disease and related dementias (ADRD).

OBJECTIVE: This study aims to compare the downstream costs and healthcare utilization associated with using low-dose computed tomography (LDCT) for lung cancer screening in patients with and without Alzheimer's disease and related dementias (ADRD). METHODS: Based on data from IBM MarketScan Commercial Claims Databases (2014-2018), we have identified four study cohorts: ADRD and non-ADRD patients who went through LDCT screening; ADRD and non-ADRD patients without LDCT screening. Annually healthcare utilization and cost were grouped into outpatient, inpatient, and pharmacy. We used difference-in-differences (DID) models to estimate the downstream healthcare utilization and cost associated with LDCT screening in both ADRD and non-ADRD population. We used a difference-in-difference-in-differences (DDD) model to explore whether LDCT screening was associated with higher downstream cost and healthcare utilization in ADRD population than non-ADRD population. RESULT: Compared to individuals without LDCT screening, LDCT screening was associated with increased outpatient visits (2.1, 95% CI 0.7, 3.4) and outpatient cost ($2301.0, 95% CI 296.2, 4305.8) in the ADRD population and increased outpatient visits (0.6, 95% CI 0.1, 1.1) in the non-ADRD population within 1 year after screening. Compared with the non-ADRD population, LDCT screening was found to be associated with an additional 1.5 (95% CI 0.2, 2.8) outpatient visits, 0.7 (95% CI 0.1, 1.3) days of inpatient stays, and $4,960.4 (95% CI 532.7, 9388.0) in overall healthcare costs within 1-year after LDCT in the ADRD population (all p < .5). CONCLUSION: The downstream cost and healthcare utilization associated with LDCT screening were found to be higher in the ADRD population compared to the average population.