ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective To explore the potential molecular mechanism of Maitong Jun'an decoction(MTJA)in the treatment of coronary heart disease based on network pharmacology,molecular docking and animal experiments.Methods The main active components and corresponding protein targets of MTJA were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and SwissTargetPrediction combined with literatures.Genes associated with myocardial infarction and heart failure in coronary heart disease were searched in DisGeNET,Genecards and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of compound targets and disease targets was obtained,and"medicine-composition-target-disease"network was constructed.The overlapping targets were imported into STRING database to construct protein-protein interaction(PPI)network.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the targets,and molecular docking studies were further conducted on the core targets and active compounds.The rat model of myocardial infarction was established.The morphological and pathological changes of heart tissue were observed by hematoxylin-eosin staining,and the expression of core target protein was detected by Western blotting.Results There were 264 nodes and 1 193 interrelationships in the"medicine-composition-target-disease"network.Quercetin and kaempferol were the key components as ranked by degree value.The proteins with high degree in PPI network were interleukin(IL)-6,IL-1β and protein kinase B 1(Akt1).GO and KEGG analyses showed that the mechanism of MTJA in the treatment of coronary heart disease mainly involved lipids and atherosclerosis,advanced glycation end product(AGE)-receptor for advanced glycation end product(RAGE)signaling pathway in diabetes complications,fluid shear stress and atherosclerosis,IL-17 signaling pathway,etc.The results of molecular docking showed that the important compounds of MTJA had strong binding ability with the core target.The results of animal experiments showed that MTJA could significantly alleviate the myocardial injury in rats with myocardial infarction,and reduce the expression levels of IL-1β and IL-6 proteins in apical tissue of rats with coronary heart disease.Conclusion MTJA may play a role in the treatment of coronary heart disease by reducing the expression levels of IL-1β and IL-6 proteins.

Objective To investigate the mechanism of Qingfei Fang(QF)protecting human bronchial epithelioid cells 16(16HBE).Methods The potential targets of QF on cellular inflammation by network and pharmacology analysis were identified.The effects of different concentrations and exposure times of QF on the relative viability of LPS induced 16HBE cells were measured by CCK8.16HBE cells were divided into control group,model group,QF group,and shPPARγ group.The control group was received no treatment,the model group was treated with 200 ng·mL-1 LPS for 24 h,the QF group was treated with 200 ng·mL-1 LPS and 40 ng·mL-1 QF for 24 h,and the shPPARγ group was treated with 40 ng·mL-1 QF for 4 h in the 16HBE-M-4 cell line before being treated with 200 ng·mL-1 LPS for 4 h.The levels of interleukin-6,interleukin-10,tumor necrosis factor-α,malondialdehyde,and superoxide dismutasein the cell culture supernatant were detected by ELISA.Polymerase chain reaction was applied to detect the mRNA levels of NF-κB p50 and p65 in cell supernatants.Western blot was applied to detect the protein expression of NF-κB p65 in 16HBE.Results Sanggenon D and Coptis chinensis bind to target protein PPARγ.Subsequent cell experiments were carried out with the concentration of 40 ng·mL-1 Qingfei Fang.Compared to the control group,cell viability reduced,levels of IL-6,TNF-αand MDA increased,and levels of IL-10 and SOD decreased significantly(P<0.05)in the model group.The levels of NF-κB p50 and p65 mRNA also increased significantly(P<0.05),indicating successful induction of an inflammatory phenotype in the model group.Compared to the model group,the levels of IL-6,TNF-α,and NF-κB in the cell culture supernatant reduced in the QF group,while the levels of IL-10 and SOD increased significantly(P<0.05).After lentivirus-mediated shPPARγ transfection,the ability of QF to reduce IL-6,TNF-α,and NF-κB p65 levels and to increase IL-10 and SOD levels were inhibited(P<0.05).Conclusion QF may exert a protective effect on 16HBE cells by upregulating PPARγ to inhibit NF-κB pathway-mediated inflammatory response and oxidative stress.

Objective To investigate the mechanism of Qingfei Fang(QF)protecting human bronchial epithelioid cells 16(16HBE).Methods The potential targets of QF on cellular inflammation by network and pharmacology analysis were identified.The effects of different concentrations and exposure times of QF on the relative viability of LPS induced 16HBE cells were measured by CCK8.16HBE cells were divided into control group,model group,QF group,and shPPARγ group.The control group was received no treatment,the model group was treated with 200 ng·mL-1 LPS for 24 h,the QF group was treated with 200 ng·mL-1 LPS and 40 ng·mL-1 QF for 24 h,and the shPPARγ group was treated with 40 ng·mL-1 QF for 4 h in the 16HBE-M-4 cell line before being treated with 200 ng·mL-1 LPS for 4 h.The levels of interleukin-6,interleukin-10,tumor necrosis factor-α,malondialdehyde,and superoxide dismutasein the cell culture supernatant were detected by ELISA.Polymerase chain reaction was applied to detect the mRNA levels of NF-κB p50 and p65 in cell supernatants.Western blot was applied to detect the protein expression of NF-κB p65 in 16HBE.Results Sanggenon D and Coptis chinensis bind to target protein PPARγ.Subsequent cell experiments were carried out with the concentration of 40 ng·mL-1 Qingfei Fang.Compared to the control group,cell viability reduced,levels of IL-6,TNF-αand MDA increased,and levels of IL-10 and SOD decreased significantly(P<0.05)in the model group.The levels of NF-κB p50 and p65 mRNA also increased significantly(P<0.05),indicating successful induction of an inflammatory phenotype in the model group.Compared to the model group,the levels of IL-6,TNF-α,and NF-κB in the cell culture supernatant reduced in the QF group,while the levels of IL-10 and SOD increased significantly(P<0.05).After lentivirus-mediated shPPARγ transfection,the ability of QF to reduce IL-6,TNF-α,and NF-κB p65 levels and to increase IL-10 and SOD levels were inhibited(P<0.05).Conclusion QF may exert a protective effect on 16HBE cells by upregulating PPARγ to inhibit NF-κB pathway-mediated inflammatory response and oxidative stress.

OBJECTIVE To investigate and analyze the operational costs and current charging policies of pharmacy intravenous admixture service （PIVAS） in China， and provide a reference for promoting high-quality and sustainable development of PIVAS. METHODS Questionnaires were distributed in 30 provinces， autonomous regions， and municipalities across the country through the “Wenjuanxing” platform from May 6th to July 1st， 2022. The operational costs， charging status and suggestions of PIVAS were investigated and analyzed. RESULTS A total of 761 PIVAS participated in the survey nationwide， including 666 tertiary medical institutions， 93 secondary medical institutions， and 2 primary medical institutions. Approximately 60.58% of PIVAS had implemented a charging system that allowed charges. Among them， most PIVAS required inspection and evaluation before charging. The annual operating cost of PIVAS in China was approximately 2 098 100 yuan， with the integrated operating cost comprising 89.36% of the total， while the dispensing cost accounted for only 10.64%. Human costs emerged as the highest annual consumption （74.20%）， followed by decoration and facility maintenance costs （4.77%） and equipment acquisition costs （3.44%）. Regarding charges for different drugs nationwide， common drugs had an average charge standard of 4.39 yuan per bag while antibacterial drugs averaged 5.01 yuan per bag； hazardous drugs had an average charge of 23.17 yuan per bag， whereas parenteral nutrition solutions averaged 38.75 yuan per bag. However， the recommended average charges of the four drugs mentioned above were 6.71， 9.63， 38.35 and 44.03 yuan per bag， respectively. CONCLUSIONS At present， there is no unified inspection and evaluation standard and charging standard in China. Moreover， the current charging standard is lower than the recommended standard. It is necessary to combine operational costs and develop more reasonable and fair charging standards.

Objective·To investigate the effects of sennoside A(SA)on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine(5-HT)and its receptor in mice with diabetes mellitus type 2(T2DM).Methods·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups,namely the model group and the model+SA group,with six mice in each group.Six C57BL/6J mice with the same genetic background were used as the control group.The control group was fed with normal diet,and the model group and the model+SA group were given intraperitoneal injection of streptozotocin(30 mg/kg)daily on the basis of high-fat diet to establish a model of T2DM.The model+SA group was given SA daily by gavage for 8 weeks,and the control group and the model group were given equal volume of distillation-distillation H2O by gavage.The body weight,fasting blood glucose(FBG)and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment.The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin(H-E)staining,and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit.Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B(HTR2B)and serotonin transporter(SERT)in thoracic aorta of mice.Results·Compared with the control group,the body weight,FBG and 2-h postprandial blood glucose in the model group increased,and glucose metabolism was disordered.The expression of HTR2B and SERT protein in thoracic aorta increased,while the concentration of 5-HT in thoracic aorta decreased.The serum 5-HT concentration increased(all P<0.05).After treatment with SA,compared with the model group,the body weight of the model+SA group decreased,and FBG and 2-h postprandial blood glucose were significantly improved.The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased,while the concentration of 5-HT increased.The serum 5-HT concentration decreased(all P<0.05).Conclusion·SA can reduce atherosclerotic plaque area in T2DM mice,which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

OBJECTIVE To explore the effects and mechanisms of cycloartenol on myocardial ischemia-reperfusion injury in mice.METHODS In vitro experiments,primary cardiomyocytes were extracted from 1-3 days SD mice.The hypoxia/reoxygenation model was established by incubating cells in a hypoxic culture box for 3 hours followed by reoxygenation in a normal culture box for 3 hours.The primary cardiomyocytes were divided into Control group,H/R group,low-dose(3 μmol·L-1)and high-dose(10 μmol·L-1)cycloartenol groups,and SB203580 group.CCK-8 was used to detect cell viability,the apoptosis rate was detected by flow cytometry,and Western blot was used to detect the expression levels of p38 MAPK and p-p38 MAPK in each group.In an in vi-vo experiment,7-week-old male C57BL/6J mice were randomly divided into a Control group,an I/R group,and three doses of cyclo-artenol(0.2,0.5,1.0 mg·kg-1)groups.The mice were continuously administered for seven days before the surgery.The model was prepared by ligation of the left anterior descending coronary artery(LAD)for 30 minutes,followed by reperfusion for 24 hours to in-duce myocardial ischemia-reperfusion injury.Left ventricular ejection fraction(LVEF),cardiac output(CO),left ventricular fractional shortening(LVFS)of each group of mice were detected by small animal ultrasound.TTC staining was used to detect the changes of is-chemic infarct size in each group.The changes of myocardial tissue in each group were observed by HE staining.The expression levels of p38 MAPK,p-p38 MAPK,IL-6 and TNF-α in myocardial tissue of mice were detected by Western blot.Serum levels of creatine ki-nase isoenzyme(CK-MB),lactate dehydrogenase(LDH),cardiac troponin I(cTnI),interleukin-6(IL-6),and tumor necrosis fac-tor-α(TNF-α)were measured using ELISA kits.RESULTS In vitro experiments demonstrated that compared with the H/R group,both the cycloartenol and SB203580 pretreatment groups showed a significant increase in myocardial cell viability and the apoptosis rate decrease,which can downregulate the protein expression level of p-p38 MAPK and decrease the ratio of p-p38 MAPK/p38 MAPK(P<0.05).In vivo experiments confirmed that compared with the I/R group,cycloartenol pretreatment significantly improved LVEF,LVFS,and CO values(P<0.05),reduce myocardial ischemic infarct size,thereby enhancing myocardial function.The protein ex-pression level of p-p38 MAPK in myocardial tissue was down-regulated,the ratio of p-p38 MAPK/p38 MAPK was decreased,and the expression levels of IL-6 and TNF-α were decreased.Additionally,cycloartenol pretreatment reduced the levels of CK-MB,LDH,cT-nI,IL-6,and TNF-α in mouse serum(P<0.05).CONCLUSION Pre-treatment with cycloartenol can protect mouse cardiac func-tion and alleviate myocardial ischemia-reperfusion injury.Its mechanism of action may be related to the inhibition of p38 MAPK phos-phorylation,reducing inflammatory reactions.

OBJECTIVE To observe the clinical efficacy of Maitong Jun'an Decoction in treating coronary heart disease(CHD)angina of qi deficiency and blood stasis type,and preliminarily elucidate its possible mechanism of action through transcriptomics meth-ods.METHODS A total of 140 patients with CHD angina of qi deficiency and blood stasis type were included and randomly divided into a treatment group and a control group,with 70 cases in each group.During the treatment period,3 patients in the control group dropped out.The control group received basic Western medicine treatment for secondary prevention of CHD,while the treatment group received Maitong Jun'an Decoction in addition to the treatment in the control group.The treatment period for both groups was 8 weeks.Before and after treatment,the patients in both groups were evaluated for the TCM syndrome score,Canadian Cardiovascular Society(CCS)angina grading,Seattle angina questionnaire(SAQ)score,self-rating anxiety scale(SAS),self-rating depression scale(SDS)score,and adverse reactions.The peripheral blood of 9 patients before and after treatment was selected for transcriptomic sequencing based on the principle of gender,age,and disease duration matching.RESULTS After treatment,the TCM syndrome scores and total scores of the 2 groups were significantly reduced(P<0.01).The treatment group was better than the control group in improving chest pain,chest tightness,shortness of breath,fatigue and total score(P<0.05,P<0.01);the overall improvement rate of CCS angina grading in the treatment group was better than that in the control group(P<0.05);the SAQ,SAS and SDS scores of the 2 groups were significantly reduced before and after treatment(P<0.01),and the SAQ score of the treatment group was improved better than that of the control group(P<0.05,P<0.01).The transcriptomics results showed that there were 862 significantly different mR-NAs before and after treatment,including 509 up-regulated and 353 down-regulated.GO analysis showed that there were 666 biologi-cal processes in the differentially expressed mRNAs,mainly including viral gene expression,translation initiation,RNA catabolism,etc.There were 112 cell components,mainly including focal adhesion,ribosome subunit,nuclear spot,etc.There were 94 molecular functions,mainly including double-stranded RNA binding,cadherin binding,transcription co-regulatory factor activity,etc.KEGG analysis showed that the differentially expressed mRNAs enriched in 20 signaling pathways,mainly including glycerophospholipid me-tabolism pathway,AMPK signaling pathway,ribosome pathway,etc.CONCLUSION Maitong Jun'an Decoction can improve clini-cal symptoms in patients with CHD angina of qi deficiency and blood stasis type.Its mechanism of action is multi-target and multi pathway,mainly related to the regulation of glycerophospholipid metabolism pathway,AMPK signaling pathway,ribosome pathway.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.