This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL). METHODS: The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis. RESULTS: A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005). CONCLUSION The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Asparaginase/therapeutic use* ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Prognosis ; Retrospective Studies ; Survival Rate ; Polyethylene Glycols

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective To observe the therapeutic effect and compatibility mechanism of Wumei Wan on diabetic gastroparesis(DGP)mice.Methods Sixty-nine C57BL/6J mice were randomly divided into normal group(12 mice)and model group(57 mice).The DGP model was constructed by 60％high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).After successful modeling,the mice in the model group were randomly divided into model group,Wumei Wan whole prescription group,Wumei Wan sour medicine group,Wumei Wan bitter medicine group,Wumei Wan sweet medicine group and Wumei Wan pungent medicine group,with nine mice in each group.After 28 days of treatment,the gastric emptying rate and small intestinal propulsion rate of mice were measured.The pathological changes of gastric antrum were observed by hematoxylin-eosin(HE)staining.The fasting blood glucose(FBS)of mice was detected by blood glucose meter.The levels of triglyceride(TG),total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)were detected by colorimetry.The contents of gastrin(GAS),motilin(MTL)and vasoactive intestinal peptide(VIP)in gastric antrum were detected by enzyme-linked immunosorbent assay(ELISA).Western Blot was used to detect the expression of Kelch-like ECH-associated protein 1(Keap-1),nuclear factor erythroid 2-related factor 2(Nrf-2),NAD(P)H:quinone oxidoreductase 1(Nqo-1)and superoxide dismutase 1(Sod-1)in gastric antrum tissue.Results(1)Compared with the normal group,the levels of serum FBS,TG,TC and LDL-C in the model group were significantly increased(P＜0.05 or P＜0.01 or P＜0.001);compared with the model group,the blood glucose level of the whole prescription group,the sour medicine group and the bitter medicine group was decreased significantly at the end of the third and fourth week(P＜0.05 or P＜0.01 or P＜0.001),the serum TG,TC and LDL-C levels of the whole prescription group were significantly decreased(P＜0.05 or P＜0.01),the serum TC level of the sour medicine group,the bitter medicine group,the sweet medicine group and the pungent medicine group was significantly decreased(P＜0.05),and only the LDL-C level of the sour medicine group was significantly decreased(P＜0.05).(2)Compared with the normal group,the glandular cells in the gastric antrum mucosa and submucosa of the model group were disordered;compared with the model group,the pathological damage of gastric antrum tissue in Wumei Wan whole prescription group was significantly improved,the recovery effect of gastric antrum tissue damage in DGP mice in the sour medicine group and the bitter medicine group was superior to that in the sweet medicine group and the pungent medicine group.(3)Compared with the normal group,the gastric emptying rate and small intestinal propulsion rate of the model group were decreased(P＜0.01 or P＜0.001);compared with the model group,the gastric emptying rate of the whole prescription group,the sour medicine group and the bitter medicine group was significantly increased(P＜0.05 or P＜0.001),and the intestinal propulsion rate of the whole prescription group,the sour medicine group,the bitter medicine group,the sweet medicine group and the pungent medicine group was significantly increased(P＜0.05 or P＜0.01 or P＜0.001).(4)Compared with the normal group,the content of VIP in the gastric antrum tissue of the model group was significantly increased(P＜0.01),and the contents of GAS and MTL were significantly decreased(P＜0.01 or P＜0.001).Compared with the model group,the content of GAS in Wumei Wan whole prescription group,the sour medicine group,the bitter medicine group and the sweet medicine group was significantly increased(P＜0.01 or P＜0.001),the content of MTL in the whole prescription group and the bitter medicine group was significantly increased(P＜0.05 or P＜0.01),and the content of VIP in gastric antrum tissue of mice in Wumei Wan whole prescription group,sour medicine group,bitter medicine group and sweet medicine group was significantly decreased(P＜0.05 or P＜0.01 or P＜0.001).(5)Compared with the normal group,the expression level of Keap-1 in the gastric antrum tissue of the model group was increased(P＜0.05),and the expressions of Nrf-2,Nqo-1 and Sod-1 were decreased(P＜0.05 or P＜0.001).Compared with the model group,the expression level of Keap-1 protein in the whole prescription group and the bitter medicine group was significantly decreased(P＜0.05 or P＜0.001),and the expression levels of Nrf-2,Nqo-1 and Sod-1 in the whole prescription group,the sour medicine group and the bitter medicine group were significantly increased(P＜0.05 or P＜0.001).Conclusion Wumei Wan can effectively regulate glucose and lipid metabolism,improve gastric antrum injury and promote gastrointestinal motility in DGP mice.The efficacy of the whole prescription is superior to that of each disassembled prescription.The mechanism may be related to the synergistic compatibility of sour medicine,bitter medicine,sweet medicine and pungent medicine,and mainly through sour medicine and bitter medicine regulating Nrf-2/Keap-1 pathway further to improve oxidative stress injury.

AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

This study aims to investigate the impact of the invasive pest Corythucha marmorata on the growth and quality of Artemi-sia argyi. The signs of insect damage at the cultivation base of A. argyi in Huanggang, Hubei were observed. The pests were identified based on morphological and molecular evidence. The pest occurrence pattern and damage mechanism were investigated. Electron microscopy, gas chromatography-mass spectrometry(GC-MS), and high performance liquid chromatography(HPLC) were employed to analyze the microstructure, volatile oils, and flavonoid content of the pest-infested leaves. C. marmorata can cause destructive damage to A. argyi. Small decoloring spots appeared on the leaf surface at the initial stage of infestation. As the damage progressed, the spots spread along the leaf veins and aggregated into patches, causing yellowish leaves and even brownish yellow in the severely affected areas. The insect frequently appeared in summer because it thrives in hot dry conditions. After occurrence on the leaves, microscopic examination revealed that the front of the leaves gradually developed decoloring spots, with black oily stains formed by the black excrement attaching to the glandular hairs. The leaf flesh was also severely damaged, and the non-glandular hairs were broken, disor-ganized, and sticky. The content of neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acids A and B, hispidulin, jaceosidin, and eupatilin at the early stage of infestation was significantly higher than that at the middle stage, and the content decreased at the last stage of infestation. The content of eucalyptol, borneol, terpinyl, and caryophyllin decreased in the moderately damaged leaves and increased in the severely damaged leaves. C. marmorata was discovered for the first time on A. argyi leaves in this study, and its prevention and control deserves special attention. The germplasm materials resistant to this pest can be used to breed C. marmorata-resis-tant A. argyi varieties.
Artemisia/chemistry* ; Plant Breeding ; Gas Chromatography-Mass Spectrometry ; Oils, Volatile/analysis* ; Chromatography, High Pressure Liquid ; Plant Leaves/chemistry*

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Objective: To investigate the predicting value of different risk prediction models for short-term death in patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and treated with extracorporeal membrane oxygenation (ECMO). Methods: This study was a retrospective case-control study. Forty patients with STEMI complicated by cardiogenic shock who hospitalized in the First Affiliated Hospital of Zhengzhou University from April 2017 to August 2021 and treated with percutaneous coronary intervention (PCI) and ECMO, were enrolled in this study. Patients were divided into survival group and death group according to their clinical outcomes at 30 days after ECMO implantation, and clinical data of the two groups were collected and analyzed. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to compare the predictive value of ACEF, AMI-ECMO, Encourage and SAVE risk scores for mortality at 30 days after ECMO implantation. According to the evaluation results of DCA, the optimal risk score was selected. Kaplan-Meier curve estimating the 30-day survival after ECMO implantation was plotted by grouping risk scores with reference to previous literatures. Results: A total of 40 patients with STEMI combined with cardiogenic shock were included, age was (57.4±16.7) years, 31 (77.5%) patients were male, there were 21 (52.5%) patients in the death group and 19 (47.5%) in the survival group. Compared with the survival group, patients in the death group had higher lactic acid values, higher proportion of anterior descending artery or left main artery lesions, and a higher proportion of acute renal failure and continuous renal replacement therapy during hospitalization (all P<0.05). Compared with survival group, ACEF, AMI-ECMO and Encourage scores were higher in death group, SAVE score was lower in death group (all P<0.05). The ROC curve analysis showed that the area under the curve (AUC) of ACEF, AMI-ECMO, Encourage and SAVE scores in predicting mortality were 0.707, 0.816, 0.757, and 0.677 respectively (P>0.05). ACEF score demonstrated the highest sensitivity (90.5%) and Encourage score exhibited the highest specificity (89.5%). DCA indicated that the AMI-ECMO and Encourage scores had the best performance in predicting the 30-day mortality after ECMO therapy. Kaplan-Meier survival curve analysis showed that the 30-day mortality after ECMO implantation increased with the increase of AMI-ECMO and Encourage scores (log-rank P≤0.001). Conclusions: The 4 scoring systems are all suitable for predicting 30-day mortality after VA-ECMO therapy in patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock. Among them, AMI-ECMO and Encourage scores have better predicting performance.
Adult ; Aged ; Case-Control Studies ; Extracorporeal Membrane Oxygenation/methods* ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention/methods* ; Retrospective Studies ; ST Elevation Myocardial Infarction/therapy* ; Shock, Cardiogenic/therapy*

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ² test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ² test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ²=6.971, P=0.008) and nCRT group (6.9% (2/29), χ²=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ²=10.881, P=0.001; χ²=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ²=6.740, P=0.009) and nCRT group (31.0% (9/29), χ²=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ²=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ²=4.976, P=0.083) and progression-free survival (χ²=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.
Adenocarcinoma/pathology* ; Adult ; Aged ; Cohort Studies ; Esophagogastric Junction/pathology* ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Propensity Score