ABSTRACT
BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.
ABSTRACT
Litter input triggers the secretion of soil extracellular enzymes and facilitates the release of carbon (C), nitrogen (N), and phosphorus (P) from decomposing litter. However, how soil extracellular enzyme activities were controlled by litter input with various substrates is not fully understood. We examined the activities and stoichiometry of five enzymes including ß-1,4-glucosidase, ß-D-cellobiosidase, ß-1,4-N-acetyl-glucosaminidase, leucine aminopeptidase and acidic phosphatase (AP) with and without litter input in 10-year-old Castanopsis carlesii and Cunninghamia lanceolata plantations monthly during April to August, in October, and in December 2021 by using an in situ microcosm experiment. The results showed that: 1) There was no significant effect of short-term litter input on soil enzyme activity, stoichiometry, and vector properties in C. carlesii plantation. In contrast, short-term litter input significantly increased the AP activity by 1.7% in May and decreased the enzymatic C/N ratio by 3.8% in August, and decreased enzymatic C/P and N/P ratios by 11.7% and 10.3%, respectively, in October in C. lanceolata plantation. Meanwhile, litter input increased the soil enzymatic vector angle to 53.8° in October in C. lanceolata plantations, suggesting a significant P limitation for soil microorganisms. 2) Results from partial least squares regression analyses showed that soil dissolved organic matter and microbial biomass C and N were the primary factors in explaining the responses of soil enzymatic activity to short-term litter input in both plantations. Overall, input of low-quality (high C/N) litter stimulates the secretion of soil extracellular enzymes and accelerates litter decomposition. There is a P limitation for soil microorganisms in the study area.
Subject(s)
Carbon , Cunninghamia , Fagaceae , Nitrogen , Phosphorus , Soil Microbiology , Soil , Soil/chemistry , Cunninghamia/growth & development , Cunninghamia/metabolism , Carbon/metabolism , Carbon/analysis , Nitrogen/metabolism , Nitrogen/analysis , Phosphorus/metabolism , Phosphorus/analysis , Fagaceae/growth & development , Fagaceae/metabolism , Leucyl Aminopeptidase/metabolism , Cellulose 1,4-beta-Cellobiosidase/metabolism , Ecosystem , Plant Leaves/metabolism , Plant Leaves/chemistry , Acetylglucosaminidase/metabolism , Acid Phosphatase/metabolism , beta-Glucosidase/metabolism , ChinaABSTRACT
Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Child , Female , Humans , Male , China , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/administration & dosage , Myalgia/chemically induced , Parents , Surveys and Questionnaires , Vaccination/adverse effects , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunologyABSTRACT
The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1ß and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.
Subject(s)
Gynostemma , Tumor Necrosis Factor-alpha , Male , Mice , Animals , Tumor Necrosis Factor-alpha/metabolism , Mice, Inbred C57BL , Lung , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/metabolism , Interleukin-6/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Lipopolysaccharides/pharmacologyABSTRACT
Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.
Subject(s)
Alkaloids , Antineoplastic Agents , Coptis , Drugs, Chinese Herbal , Plants, Medicinal , Glycosides/chemistry , Medicine, Chinese Traditional , Tandem Mass Spectrometry/methods , Coptis chinensis , Drugs, Chinese Herbal/chemistry , Alkaloids/analysis , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Water , Chromatography, High Pressure Liquid/methods , Coptis/chemistryABSTRACT
Graphitized carbon black (GCB) in the traditional QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used to remove the interfering substance chlorophyll in vegetable and fruit samples for pesticide residues determination. However, it not only adsorbs pigments, but also adsorbs some planar and aromatic pesticides. In order to solve the shortcoming, a core-shell magnetic molecularly imprinted polymer (Fe3O4@MIP) that can specifically recognize and adsorb chlorophyll was synthesized, and an advanced QuEChERS method with the Fe3O4@MIP as a purification material was developed. This advanced method presents detection that is highly sensitive, specific, and reproducible for planar and aromatic pesticides. The limits of detection (LOD) ranged from 0.001-0.002 mg kg-1, and the limit of quantification (LOQ) was 0.005 mg kg-1. The recovery for the planar and aromatic pesticides was within 70-110% with the associated relative standard deviations < 15% in leek samples by the advanced QuEChERS method. However, in the traditional QuEChERS method with GCB, the recovery of most planar and aromatic pesticides was <60%. It may also be useful for the determination of other pesticides in vegetable samples with quick and easy sample purification.
ABSTRACT
BACKGROUND: Long waiting time in hospital leads to patient's low satisfaction. In addition to reducing the actual waiting time (AWT), we can also improve satisfaction by adjusting the expected waiting time (EWT). Then how much can the EWT be adjusted to attribute a higher satisfaction? METHODS: This study was conducted though experimental with hypothetical scenarios. A total of 303 patients who were treated by the same doctor from August 2021 to April 2022 voluntarily participated in this study. The patients were randomly divided into six groups: a control group (n = 52) and five experimental groups (n = 245). In the control group, the patients were asked their satisfaction degree regarding a communicated EWT (T0) and AWT (Ta) under a hypothetical situation. In the experimental groups, in addition to the same T0 and Ta as the control group, the patients were also asked about their satisfaction degree with the extended communicated EWT (T1). Patients in five experimental groups were given T1 values with 70, 80, 90, 100, and 110 min respectively. Patients in both control and experiment groups were asked to indicate their initial EWT, after given unfavorable information (UI) in a hypothetical situation, the experiment groups were asked to indicate their extended EWT. Each participant only participated in filling out one hypothetical scenario. 297 valid hypothetical scenarios were obtained from the 303 hypothetical scenarios given. RESULTS: The experimental groups had significant differences between the initial indicated EWT and extended indicated EWT under the effect of UI (20 [10, 30] vs. 30 [10, 50], Z = -4.086, P < 0.001). There was no significant difference in gender, age, education level and hospital visit history (χ2 = 3.198, P = 0.270; χ2 = 2.177, P = 0.903; χ2 = 3.988, P = 0.678; χ2 = 3.979, P = 0.264) in extended indicated EWT. As for patient's satisfaction, compared with the control group, significant differences were found when T1 = 80 min (χ2 = 13.511, P = 0.004), T1 = 90 min (χ2 = 12.207, P = 0.007) and T1 = 100 min (χ2 = 12.941, P = 0.005). When T1 = 90 min, which is equal to the Ta, 69.4% (34/49) of the patients felt "very satisfied", this proportion is not only significantly higher than that of the control group (34/ 49 vs. 19/52, χ2 = 10.916, P = 0.001), but also the highest among all groups. When T1 = 100 min (10 min longer than Ta), 62.5% (30/48) of the patients felt "very satisfied", it is significantly higher than that of the control group (30/ 48 vs. 19/52, χ2 = 6.732, P = 0.009). When T1 = 80 min (10 min shorter than Ta), 64.8% (35/54) of the patients felt "satisfied", it is significantly higher than that of the control group (35/ 54 vs. 17/52, χ2 = 10.938, P = 0.001). However, no significant difference was found when T1 = 70 min (χ2 = 7.747, P = 0.052) and T1 = 110 min (χ2 = 4.382, P = 0.223). CONCLUSIONS: Providing UI prompts can extend the EWT. When the extended EWT is closer to the AWT, the patient's satisfaction level can be improved higher. Therefore, medical institutions can adjust the EWT of patient's through UI release according to the AWT of hospitals to improve patient's satisfaction.
Subject(s)
Patient Satisfaction , Waiting Lists , Humans , Control Groups , Educational Status , Personal SatisfactionABSTRACT
Oxidative stress caused by environmental exposures results in numerous skin diseases. Phloretin (PHL) is often used to relieve various skin symptoms, however, precipitation or crystallization of PHL in aqueous systems limits its ability to diffuse through the stratum corneum, making it difficult to exert effect at the target. To address this challenge, we herein report a method for the generation of core-shell nanostructure (G-LSS) via the growth of sericin crust around gliadin nanoparticle as a topical nanocarrier of PHL to improve its cutaneous bioavailability. Physicochemical performance, morphology, stability, and antioxidant activity of the nanoparticles were characterized. G-LSS-PHL exhibited uniformed spherical nanostructures with the robust encapsulation on PHL (â¼90 %). This strategy protected PHL from UV-induced degradation, facilitating to inhibit erythrocyte hemolysis and quench free radicals in a dose-dependent manner. Transdermal delivery experiments and porcine skin fluorescence imaging indicated that G-LSS facilitated the penetration of PHL across the epidermis layer of skin to reach deep-seated sites, and promoted cumulative turnover of PHL with a 2.0-fold increase. Cell cytotoxicity and uptake assay confirmed that as-prepared nanostructure was nontoxic to HSFs, and promoted cellular absorption of PHL. Therefore, this work opened up new promising avenues for developing robust antioxidant nanostructure for topical applications.
Subject(s)
Nanoparticles , Sericins , Animals , Swine , Antioxidants/pharmacology , Antioxidants/metabolism , Sericins/pharmacology , Gliadin , Phloretin/pharmacology , Phloretin/chemistry , Skin , Administration, Cutaneous , Nanoparticles/chemistryABSTRACT
The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.
Subject(s)
Gynostemma , Hypolipidemic Agents , Saponins , Alanine Transaminase/analysis , Animals , Aspartate Aminotransferases/analysis , Bile Acids and Salts/blood , Bilirubin/blood , Cholesterol, LDL/blood , Diet, High-Fat/adverse effects , Gynostemma/chemistry , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Lipoproteins, HDL/blood , Liver/chemistry , Liver/metabolism , Malondialdehyde/analysis , Peroxisome Proliferator-Activated Receptors/analysis , Rats , Rats, Sprague-Dawley , Saponins/pharmacology , Saponins/therapeutic use , Superoxide Dismutase , Triglycerides/blood , Trisaccharides/pharmacology , Trisaccharides/therapeutic useABSTRACT
BACKGROUND: Renal cell carcinoma (RCC) is associated with a high risk of recurrence. Although RCC has been shown to impose a substantial burden on patients, little is known about the incremental clinical and economic burden attributable to disease recurrence. With recent advances in the RCC-therapeutic landscape, including adjuvant therapies, it is important to quantify the clinical and economic burden associated with RCC recurrence to better evaluate the potential impact of treatment in this patient population. OBJECTIVE: To quantify the incremental clinical and economic burden associated with disease recurrence among patients with intermediate high-risk and high-risk RCC postnephrectomy. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2016) were used to identify patients with newly diagnosed, intermediate high-risk or high-risk RCC following nephrectomy. Patients with a diagnosis of metastatic disease or repeat nephrectomy or initiating a systemic treatment for advanced RCC were grouped as the recurrence cohort; patients without evidence of recurrence were grouped as the cohort without recurrence. Health care resource utilization (HRU), health care costs (2019 US dollars), and overall survival (OS) were compared between cohorts with and without recurrence, adjusting for demographic and clinical characteristics. RESULTS: A total of 269 patients with recurrence and 374 patients without recurrence were analyzed. Mean age was 75.2 and 75.7 years (P = 0.383), respectively, and 64.7% and 57.8% (P = 0.076) of patients were male, respectively. Median follow-up duration was 17 and 28 months, respectively. Patients with recurrence had a significantly shorter OS relative to patients without recurrence (adjusted hazard ratio = 6.00; 95% CI = 4.24-8.48; P < 0.001). Additionally, compared with patients without recurrence, patients with recurrence had significantly more inpatient admissions (0.16 vs 0.04 admissions per person-month [PM]; adjusted incidence rate ratio [aIRR] = 3.88; 95% CI = 3.12-4.81), outpatient visits (3.06 vs 1.77 visits per PM; aIRR = 1.68; 95% CI = 1.56-1.81), emergency department visits (0.10 vs 0.05 visits per PM; aIRR = 2.11; 95% CI = 1.66-2.68), and days hospitalized (1.40 vs 0.35 days per PM; aIRR = 6.73; 95% CI = 4.95-9.15) per patient per month (all P < 0.001). Adjusted mean monthly health care costs per patient were significantly higher among patients with recurrence vs patients without recurrence (differences of all-cause total costs, total medical costs, and pharmacy cost per month: $6,320, $4,924, and $1,387; all P < 0.001). CONCLUSIONS: RCC recurrence is associated with a significant increase in mortality, HRU, and health care costs, highlighting the substantial unmet need in patients with intermediate high-risk and high-risk RCC postnephrectomy when adjuvant therapies are not widely available. DISCLOSURES: Dr Sundaram is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in AbbVie, Abbott, Johnson & Johnson, Bristol Myers Squibb, and Merck & Co., Inc. Dr Bhattacharya is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in Merck & Co., Inc. Dr Adejoro and Dr Rogerio were employees of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc. at the time of study conduct. Dr Adejoro holds stock in Johnson & Johnson. Dr Song, Dr Zhang, Mr Carley, and Dr Signorovitch are employees of Analysis Group, Inc., a consulting firm that received funding from Merck & Co., Inc. for the conduct of this research. Ms Zhu was an employee of Analysis Group, Inc. at the time of study conduct. Dr Haas is a Professor of Medicine at the Perelman School of Medicine, University of Pennsylvania and also serves on the advisory board for Aveo, Calithera and Exelixis, Co. Financial support for this study was provided by Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Aged , Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/surgery , Female , Financial Stress , Health Care Costs , Humans , Kidney Neoplasms/surgery , Male , Medicare , Neoplasm Recurrence, Local/epidemiology , Nephrectomy , Retrospective Studies , United States/epidemiologyABSTRACT
INTRODUCTION/AIMS: Hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) progressively affects patients' functionality and compromises health-related quality of life (HRQL). The aim of this study was to quantify the projected long-term treatment effects of inotersen vs placebo on HRQL measures. METHODS: The inotersen phase 2/3 randomized, double-blind, placebo-controlled trial NEURO-TTR (NCT01737398, 65 weeks) and its subsequent open-label extension (OLE; NCT02175004, 104 weeks) included 172 (112 inotersen and 60 placebo) patients. Placebo double-blind period and overall inotersen-inotersen (double-blind/OLE) treatment period (170 weeks) data were used to extrapolate the long-term placebo-placebo effect using mixed-effects models with repeated measures. Changes from baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) and 36-Item Short Form Health Survey version 2 (SF-36v2) in hATTR-PN were estimated. Differences in changes were compared between the inotersen-inotersen and extrapolated placebo-placebo arms. RESULTS: Inotersen-inotersen patients maintained their HRQL with an observed change ranging from 10.3% improvement (Norfolk QoL-DN item "Pain kept you awake at night") to 11.6% deterioration (SF-36v2 Activities of Daily Living subdomain). The extrapolated placebo-placebo results suggest greater deterioration over time compared with inotersen-inotersen treatment on Norfolk QoL-DN total score (23.6; 95% confidence interval [CI], 8.9-38.3; P < .01), Activities of Daily Living (4.6; 95% CI, 2.0-7.3; P < .001), and "Pain kept you awake at night" (1.2; 95% CI, 0.4-1.9; P < .01). Similarly, greater deterioration was expected for the SF-36v2 Physical Component Summary (8.0; 95% CI, 3.2-12.8, P < .01), Bodily Pain (7.8; 95% CI, 2.0-13.5; P < .01), and Physical Functioning (10.6; 95% CI, 5.5-15.6; P < .0001). DISCUSSION: Long-term (>3 years) inotersen treatment was associated with slowing and, in some domains, halting of deterioration in key HRQL outcome measures, particularly physical functioning and pain.
Subject(s)
Amyloid Neuropathies, Familial , Diabetic Neuropathies , Polyneuropathies , Activities of Daily Living , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/drug therapy , Diabetic Neuropathies/complications , Humans , Oligonucleotides , Pain/complications , Polyneuropathies/complications , Polyneuropathies/drug therapy , Prealbumin/therapeutic use , Quality of LifeABSTRACT
BACKGROUND: Whether combined CsA with androgen therapy was superior to androgen therapy alone in NSAA remains controversial. This study aimed to assess the efficacy and safety of combined therapy versus androgen therapy for NSAA patients using a meta-analytic approach. METHODS: An electronic database of PubMed, EmBase, Cochrane library, CNKI, VIP, and Wanfang was systematically searched for randomized controlled trials (RCTs) from their inception to February 2020. The primary endpoint was effective rate, while the secondary endpoints included white blood cell (WBC), hemoglobin, platelet, and potential adverse events. The pooled results from included trials were calculated with the random-effects model. RESULTS: Forty-three RCTs recruited 2610 NSAA patients for the final quantitative meta-analysis. We noted that combined therapy was associated with an increased incidence of effective rate than androgen therapy alone (relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.29-1.41; P < 0.001). Moreover, patients treated with combined therapy were associated with higher WBC (weighted mean difference [WMD]: 1.22; 95%CI: 0.94-1.49; P < 0.001), hemoglobin (WMD: 12.93; 95%CI: 8.86-17.01; P < 0.001), and platelet (WMD: 8.65; 95%CI: 7.05-10.24; P < 0.001). Finally, the pooled incidence of hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage were 0.35 (95%CI: 0.22-0.48), 0.24 (95%CI: 0.15-0.32), 0.22 (95%CI: 0.10-0.35), 0.19 (95%CI: 0.14-0.25), and 0.06 (95%CI: 0.01-0.11), respectively. CONCLUSIONS: This study found that combined CsA with androgen therapy was superior to androgen therapy alone for Chinese patients with NSAA, and the most common adverse of combined therapy included hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage.
Subject(s)
Anemia, Aplastic , Cyclosporine , Adult , Androgens/adverse effects , Anemia, Aplastic/drug therapy , Cyclosporine/adverse effects , Hirsutism , Humans , Hyperplasia , Randomized Controlled Trials as TopicABSTRACT
Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 µmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 µmol·L~(-1).
Subject(s)
Antineoplastic Agents , Polyketides , Coptis chinensis , Endophytes/chemistry , Fungi , Polyketides/chemistryABSTRACT
OBJECTIVE: To verify the efficacy of glucocorticoids, chloroquine and vitamin A in the treatment of cytokine release syndrome (CRS), and to investigate the underlying mechanisms, based on network pharmacology. METHODS: We used network pharmacology analysis and found 20 co-targeted genes of glucocorticoids, chloroquine, vitamin A and CRS. The pharmacological functions and therapeutic pathways of the genes were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The candidate naturally bioactive compounds against the key genes were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The anti-inflammatory activity of luteolin was assessed by real-time polymerase chain reaction. RESULTS: Among the 20 co-targeted genes of glucocorticoids, chloroquine and vitamin A, interleukin 10 (IL-10), interleukin 2 (IL-2), interleukin 4 (IL-4) and tumor necrosis factor-α (TNF-α) were the key cytokines against CRS. The key pathway involved in the pharmacological mechanism could be cytokine-cytokine receptor interaction pathway, T cell receptor signaling pathway, Janus Kinase-signal transducer and activator of transcription signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling pathway. Luteolin targeted by IL-10, IL-4, IL-2 and TNF-α could be one candidate drug for the treatment of CRS. CONCLUSION: This study comprehensively elucidates the pharmacological mechanism for the treatment of CRS and provides a new method for the discovery of drugs for this disease.
Subject(s)
Drugs, Chinese Herbal , Glucocorticoids , Chloroquine/pharmacology , Cytokine Release Syndrome , Drugs, Chinese Herbal/pharmacology , Humans , Interleukin-10 , Interleukin-2 , Interleukin-4 , Luteolin , Molecular Docking Simulation , Network Pharmacology , Tumor Necrosis Factor-alpha/metabolism , Vitamin AABSTRACT
A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 µmol·L~(-1), suggesting its potential anti-inflammatory activity.
Subject(s)
Plants, Medicinal , Polyketides , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Aspergillus/chemistry , Coptis chinensis , Polyketides/pharmacologyABSTRACT
The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS~E) technology was employed to compare the chemical components between the aerial and underground parts of Coptis chinensis samples from different batches. According to the retention time, molecular ion peak, and LC-MS~E fragment information of the reference substances and available literature, we identified a total of 40 components. Thirty-three and 31 compounds were respectively identified in the underground part(taproots) and the aerial part(stems and leaves) of C. chinensis. Among them, 24 compounds, including alkaloids(e.g., berberine and jatrorrhizine) and phenolic acids(e.g., chlorogenic acid, quinic acid, and tanshinol), were common in the two parts. In addition, differential components were also identified, such as magnoline glucoside in the underground part and(±) lariciresionol-4-ß-D-glucopyranoside in the aerial part. The analysis of fragmentation pathways based on spectra of reference substances indicated the differences among samples of different batches. Furthermore, we performed the principal component analysis(PCA) for the peak areas of C. chinensis in different batches. The results showed that the underground part and the aerial part were clearly clustered into two groups, indicating that the chemical components contained in the two parts were different. Furthermore, the results of partial least squares discriminant analysis(PLS-DA) identified 31 differential compounds(VIP value>1) between the underground part and the aerial part, mainly including alkaloids, phenolic acids, lignans, and flavonoids. This study proves that C. chinensis possesses great development potential with multiple available compounds in stems and leaves. Moreover, it sheds light on for the development and utilization of non-medicinal organs of C. chinensis and other Chinese medicinal herbs.
Subject(s)
Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Coptis chinensis , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , TechnologyABSTRACT
This study discovered that the resolution of 3,5-O-dicaffeoylquinic acid(isochlorogenic acid A) in the content determination method of Chrysanthemi Flos in Chinese Pharmacopoeia(ChP)(2020 edition) was poor, which affected accurate quantification. We tested the method in ChP with chromatographic columns of seven brands to clarify the problems in the existing method, optimized the chromatographic conditions by adjusting the mobile phase composition and elution ratio and replacing the chromatographic column packing, and carried out the reproducibility assay for the new method. The two methods were compared for the content determination results of Chrysanthemi Flos prepared from six different varieties. As evaluated by the resolution based on different chromatographic columns of seven brands, the existing method failed to separate isochlorogenic acid A and isochlorogenic acid D well. The peaks of the two components were not completely separated on three chromatographic columns, and isochlorogenic acid A and isochlorogenic acid D generated a co-effluent peak in the other four columns. Isochlorogenic acid A and isochlorogenic acid D could be completely separated under the optimized chromatographic conditions. The difference in the peak areas of isochlorogenic acid A+isochlorogenic acid D obtained by the optimized method and the method in ChP was not significant, with deviation less than 3.0%, which further proved that the result measured by the method in ChP was the co-effluent of isochlorogenic acid A and isochlorogenic acid D. The optimized method can ensure the accurate quantification of isochlorogenic acid A. The existing content determination method of Chrysanthemi Flos has the problem of poor resolution. It is recommended to revise the chromatographic conditions for the content determination method of Chrysanthemi Flos to improve the resolution of isochlorogenic acid A and ensure its accurate quantification.
Subject(s)
Drugs, Chinese Herbal , China , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Flowers/chemistry , Reproducibility of ResultsABSTRACT
Mangroves are widely distributed in the upper part of tropical and subtropical intertidal zones, with the characteristics of high productivity and fast deposition rate. Under the combined action of its own growth and microorganisms, mangroves capture, transform and store CO2 in the atmosphere into coastal sediment for a long time, and export some organic carbon from the coastal zone to the offshore and ocean, which is of great significance to prevent coastal erosion and organic carbon burial. In recent years, with the worldwide problems caused by global warming, the concept of carbon neutrality has been widely proposed. Mangroves have attracted extensive attention due to their role in regulating the global carbon cycle. This viewpoint discusses the importance of mangroves to human beings, their role in carbon sequestration and nutrient cycling, their ability to capture CO2, and their carbon sequestration functions and mechanisms, aiming to provide reference for the protection and rational utilization of mangrove resources.
Subject(s)
Carbon Sequestration , Carbon , Ecosystem , Global Warming , Humans , WetlandsABSTRACT
This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks (P = .007), 25.40% increased for times of washing hands (P = .01), and 20.90% increased for times of wearing gloves (P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.
Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , China/epidemiology , Health Behavior , Health Personnel , Humans , SARS-CoV-2 , VaccinationABSTRACT
O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL)-an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.