OBJECTIVE To identify the chemical components of Shenbai Jiedu Decoction(SBJDD),a traditional Chinese medi-cine(TCM)prescription clinically used for the treatment of colorectal adenoma(CRA),and explore the potential mechanism of SBJDD preventing and treating CRA carcinogenesis.METHODS An ultra-high performance liquid chromatography-time of flight-mass spectrometry(UPLC-Q-TOF-MS)method was established to detect the chemical components in the decoction of SBJDD and the plas-ma samples of rats after administration with SBJDD.Based on the network pharmacological method,SBJDD was screened for the poten-tial active ingredients at different stages of CRA carcinogenesis,and the mechanism of the anti-cancer effect of SBJDD was explored.In vitro experiments were also carried out to verify the mechanism of anti-colorectal cancer(CRC)action of SBJDD.RE-SULTS The detection data of UPLC-Q-TOF-MS showed that 152 components were found from SBJDD water extraction.41 chemical compounds were identified in plasma samples from rats administrated with SBJDD.Network pharmacology analysis indicated that during the CREI stage,the potential active ingredients in SBJDD,including epiberberine,and kushenol H,might affect target proteins such as PIK3CA,MAPK3 and PIK3CB.This,in turn,can influence signaling pathways like PI3K-AKT and Ras signaling pathways,and regulate biological processes like protein phosphorylation,and signal transduction.During the CRA stage,the potential active ingredi-ents from SBJDD,such as 3,7-dihydroxycoumarin,palmatine,and kushenol A,might affect target proteins such as AKT and EGFR.This can regulate the negative regulation of apoptotic process,and positive regulation of cell proliferation,and modify HIF-1,and Rap1 signaling pathways.During the progression of CRA carcinogenesis,potential active ingredients such as 3,7-dihydroxycouma-rin may interact with TP53,and impact the PI3K-AKT,and Thyroid hormone signaling pathways to regulate biological processes,in-cluding positive regulation of transcription from RNA polymerase Ⅱ promoter,and negative regulation of apoptotic process.In the CRC stage,core ingredients like p-coumaric acid may bind with proteins such as PRKCB.This binding may impact the signaling pathways that negatively affect EGFR tyrosine kinase inhibitor resistance,and PI3K-AKT signaling pathways.Additionally,it may regulate bio-logical processes,including negative regulation of apoptotic process,signal transduction,and protein phosphorylation.In vitro experi-ment results indicated that SBJDD inhibited the proliferation of HT29 cells and suppressed the expression of EGFR and PKC proteins.CONCLUSION The UPLC-Q-TOF-MS method is established to effectively separate the chemical constituents in SBJDD,which are mainly composed of alkaloids,organic acids and flavonoids components.Components from SBJDD dock with different targets during the carcinogenesis process of CRA and regulate cancer-related signaling pathways to exert therapeutic effects.

Sleep apnea causes cardiac arrest, sleep rhythm disorders, nocturnal hypoxia and abnormal blood pressure fluctuations in patients, which eventually lead to nocturnal target organ damage in hypertensive patients. The incidence of obstructive sleep apnea hypopnea syndrome (OSAHS) is extremely high, which seriously affects the physical and mental health of patients. This study attempts to extract features associated with OSAHS from 24-hour ambulatory blood pressure data and identify OSAHS by machine learning models for the differential diagnosis of this disease. The study data were obtained from ambulatory blood pressure examination data of 339 patients collected in outpatient clinics of the Chinese PLA General Hospital from December 2018 to December 2019, including 115 patients with OSAHS diagnosed by polysomnography (PSG) and 224 patients with non-OSAHS. Based on the characteristics of clinical changes of blood pressure in OSAHS patients, feature extraction rules were defined and algorithms were developed to extract features, while logistic regression and lightGBM models were then used to classify and predict the disease. The results showed that the identification accuracy of the lightGBM model trained in this study was 80.0%, precision was 82.9%, recall was 72.5%, and the area under the working characteristic curve (AUC) of the subjects was 0.906. The defined ambulatory blood pressure features could be effectively used for identifying OSAHS. This study provides a new idea and method for OSAHS screening.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Humans ; Hypertension/complications* ; Polysomnography ; Sleep Apnea, Obstructive/diagnosis*

Objective:To evaluate the efficacy of Sun's sequential therapy (SST) of Chinese Medicine on allergic rhinitis with lung deficiency and cold syndrome.Methods:A total of 60 AR patients with lung deficiency and cold syndrome in otolaryngology clinic of Guang'anmen Hospital, from January to July 2020, who met the inclusion criteria, were randomly divided into 2 groups according to the random number table method, with 30 patients in each group. The Traditional Chinese Medicine (TCM) group was treated with oral Yupingfeng Powder and Cang'erzi Powder and the SST group was treated with oral and nasal steaming of Yupingfeng Powder and Cang'erzi Powder. Both groups were treated for 14 days. The clinical symptoms were scored before and after treatment, and the Nasal mucosa eosinophil (EOS) count was graded by Sheldon method to evaluate the clinical efficacy.Results:Twenty five patients in the SST group and 28 in the TCM group were analyzed. The total effective rate was 88.0% (22/25) in the SST group and 89.3% (25/28) in the TCM group, and there was no significant difference between the two groups ( χ2=2.83, P=0.883). The scores of nasal obstruction, runny nose, sneeze and total score in the SST group were significantly lower than those in the TCM group ( P<0.01), and the difference of Nasal mucosa EOS grade in SST group (2.76±0.27 vs. 1.52±0.36) was significantly higher than that of the TCM group ( P=0.01). Conclusion:The SST of Chinese medicine can improve the symptoms of nasal congestion, runny nose and sneezing in AR patients with lung deficiency and cold syndrome, and reduce the distribution of Nasal mucosa EOS.

The blood-brain barrier (BBB) constitutes a major obstacle to effective delivery of drugs to the brain. Recent technological advances have led to improvements in brain-targeted drug delivery. In this review, we summarize existing technologies for efficient drug delivery across the BBB. We discuss the mecha-nisms of current BBB-based drug delivery strategies and introduce prospects for application in brain-targeted delivery of traditional Chinese medicine. We highlight the use of physical techniques for brain-targeted drug delivery, including electroporation, ultrasound, magnetophoresis, microneedles, microwaves, and laser. The characteristics of these techniques and relevant studies employing these approaches are discussed. In general, microneedles, lasers, ultrasound, electroporation, magnetophoresis, and microwaves are effective for drug delivery across the BBB. Notably, the synergistic effects of multiple approaches are superior to the additive effects of each technique in isolation. Our review provides guidance for the practical application of brain-targeted drug delivery techniques in an efficient and safe manner.

Objective To develop a method for the determination of five furostanol saponins(timosaponin N,timosaponin L, timosaponin BⅡ,25R-timosaponin BⅡ,and 25S-officinalisnin-Ⅰ)in rhizome and fibrous root of Anemarrhena asphodeloides Bge. by HPLC with the charged aerosol detector(CAD). Methods The analysis was performed on TechMate C18-ST-II(250 mm×4.6 mm,5μm)with acetonitrile:water(22:78,V/V),the flow rate of 1.0 ml/min and column temperature at 30℃. The Corona parameters were as follows:sampling rate 10 Hz,filter 5 s,and the nebulizer temperature 55℃. Results The approach showed good linearity for five saponins. The correlation coefficients(r2)for calibration curves varied from 0.9992 to 0.9998. The limits of detection(LOD)were 0.28,0.92,0.92,0.92 and 0.92 ng for five steroidal saponins,respectively. The limits of quantitation(LOQ)were found to be 0.92, 2.77,2.77,2.77 and 2.76 ng,respectively. RSD calculated from peak area of precision,repeatability and stability in 48 h were all less than 3.0%. The average recoveries of timosaponin N,timosaponin L,timosaponin BⅡ,25R-timosaponinBⅡ,and 25S-officinalis-nin-Ⅰwere 98.17%,101.37%,98.53%,97.63%,and 98.17%,respectively. Conclusion The developed method is accurate,reli-able,which could be applied to the quality control of multiple components in A. asphodeloides Bge.

Objective To design and synthesize compounds with protein tyrosine kinase(PTK)inhibitory activity with L029 as the lead compound. Methods L029 derivatives were designed and synthesized from L029 by reduction and/or substitution with the 3-dimethylamino-1-propyl,methyl acetate,methyl propionate in its active H and other sites. PTK activity was measured by enzyme-linked immunosorbent assay(ELISA). The inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Re-sults Five target compounds were synthesized and their structures were confirmed by 1H NMR and MS. Three compounds T2,T3 and T5 were screened out with strong PTK inhibitory activity. Conclusion The synthetic routes of the target compounds are simple with mild reaction condition,and 3 compounds show strong inhibitory activity by ELISA. These results can provide reference for the further design and synthesis of this kind of molecules.

Objective To design and synthesize novel 2-indolone derivatives as the c-Met kinase inhibitors. Methods With c-Met kinase inhibitor SU11274 as lead compound,a series of 2-indolone derivatives were designed according to the concept of bioiso-sterism. Then the target compounds(10a-10r)were synthesized from 2-indolone through 5-chlorosulfonation with chlorosulfonic acid, sulfonamidation with intermediate 3,condensation with 6a-6h,7a-7h and 4a-4b,respectively. Their inhibitory activity against c-Met and proliferation of MCF-7 cells were evaluated. Results and Conclusion The designed compounds were successfully prepared and their structures were confirmed by 1H NMR and ESI-MS. Some compounds had certain inhibitory activity against c-Met and prolif-eration of MCF-7 cells. An initial structure-activity relationship analysis of these compounds was performed to provide useful informa-tion for further optimization of their structures.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Objective The aim of this study was to investigate the effect of hepatitis C virus (HCV) replication on expression of silent information regulator 1 (SIRT1) and glucose metabolism of hepatocytes using Huh 7.5 cells harboring HCV replicon.Methods The level of reactive oxygen species (ROS),value of nicotinamide adenine dinucleotide (NAD+)/reduced form of nicotinamide adenine dinucleotide (NADH) was detected by flow cytometry and chromatometry.The activity,mRNA expression,and protein level of SIRT1 were detected by a scintillation counter,real-time fluorescence quantitative polymerase chain reaction (RT-PCR),and Western blot,respectively.Glucose uptake by hepatocytes and gluconeogenesis were detected using radioactive isotope method and glucose oxidase method.The mRNA levels of SIRT1 downstream glucose-metabolism genes were measured by RT-PCR.Measurement date were compared by t test.Results In replicon cells,the level of ROS (3.8±0.5 vs 1.0±0.2; t=12.736,P＜0.01) was increased and the value of NAD+/NADH (0.03±0.01 vs 0.12±0.03; t=6.971,P＜0.01) decreased compared with Huh 7.5 cells.The activity (0.3±0.1 vs 1.0±0.2; t=7.668,P＜0.01),mRNA expression(0.4±0.1 vs 1.0± 0.3; t=4.648,P＜0.01) and protein level(0.3±0.1 vs 0.8±0.2; t=5.941,P＜0.01) of SIRT1 were reduced.Inhibition of SIRT1 not only increased insulin receptor substrate-1 (IRS-1) phosphorylation (0.7±0.2 vs 0.4±0.1; t=3.286,P＜0.01),decreased protein kinase B (Akt) phosphorylation (0.3 ± 0.1 vs 0.6 ± 0.2; t=3.286,P＜0.01),down regulated cell surface expression of glucose transporler 2 (GLUT2,0.4±0.1 vs 1.0 ± 0.2; t =6.573,P＜0.01) and suppressed cellular glucose uptake (count per minute:4600±500 vs 21 000±4600; t=8.682,P＜0.01); but also decreased phosphorylation of forkhead box O1 (FoxO1,0.2＝0.1 vs 0.5±0.1; t=5.196,P＜ 0.01),up-regulated phosphoenolpyruvate carboxykinase (PEPCK,2.8±0.6 vs 1.0±0.3; t=6.573,P＜0.01) and glucose 6-phosphatase (2.6±0.5 vs 1.0±0.2; t=7.278,P＜0.01) genes,and promoted glucose production (2.5±0.5 vs 1.0±0.2; t=5.543,P＜0.01).Conclusions HCV replication decreases NAD+/NADH ratio,which might down-regulate the activity and the expression of SIRT1,leading to changes in the expression profile of glucose metabolism related genes and causing glucose metabolism disorders of hepatocytes by a decrease in glucose uptake and an increase in glucose production,and promotes HCV replication.