AIM To investigate the flavor technology for Jiannaoning Mixture based on electronic tongue combined with preference index.METHODS Artificial sensory evaluation method was employed to screen the type of flavor agents,electronic tongue was applied to screening the consumption of flavor agents,and double-bottle preference test was adopted in the analysis of effects of rat gender and body weight on taste sensitivity,after which acceleration test was conducted.RESULTS Sucrose,stevioside and xylitol were taken as flavor agents,whose optimal consumptions were 15%,0.08%and 15%,respectively.Male rats demonstrated stable taste perception with the body weights of 220-280 g,and 0.08%stevioside displayed the best flavoring effect.After placed under accelerated condition for 3 months,the preparation exhibited stable appearance,pH value and contents of lobetyolin,salvianolic acid B,schizandrin,ruscogenin.CONCLUSION This stable and reliable method can provide reference for improving the terrible tastes of Jiannaoning Mixture and other oral liquid preparations of traditional Chinese medicines.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective To investigate the efficacy and safety of Urinary kallidinogenase(UK)combined with butylphthalide in patients with acute cardioembolic stroke(ACS).Methods A retrospective collection was performed for ACS patients diagnosed and treated in Hangzhou First People's Hospital from May 2022 to April 2023.According to the treatment protocol,ACS patients were divided into UK group and Butylphthalide+UK group.The clinical efficacy,neurological function,serum indexes(Hcy,NT-proBNP and VEGF)and prognosis of the two groups were compared after 2 weeks of treatment.Results A total of 86 ACS patients were included in the study,including 43 in the UK group and 43 in the Butylphthalide+UK group.After treatment,the total effective rate of treatment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05),and there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).In addition,the expression levels of Hcy and NT-proBNP in ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05),while the expression levels of VEGF were significantly higher than those in the UK group(P<0.05).The NIHSS score and mRS score of ACS patients in the Butylphthalide+UK group were significantly lower than those in the UK group(P<0.05).The rate of collateral circulation establishment in the Butylphthalide+UK group was significantly higher than that in the UK group(P<0.05).Conclusion Butaphthalide combined with UK has significant efficacy and high safety in ACS patients,which may be achieved by regulating the expression levels of serum Hcy,NT-proBNP and VEGF,thereby improving neurological function and promoting the establishment of collateral circulation.

Objective To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. Methods A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. Results A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. Conclusions Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ² = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.
Adenosine Diphosphate/pharmacology* ; Adenosine Triphosphate ; Animals ; Molluscacides/pharmacology* ; Silica Gel/pharmacology* ; Snails ; Streptomyces ; Water

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Hot melt pressure-sensitive adhesive(HMPSA) has broad application potential in the field of traditional Chinese medicine(TCM) plasters due to its high drug loading, weak skin irritation, satisfactory adhesion, etc. compared with rubber plasters.However, the structure of HMPSA is prone to suffer from the damage caused by volatile oils in TCM plasters. In view of this, a kind of HMPSA with a stable structure was prepared by physical blending of DINCH, polypropylene wax and liquid rubber(LIR) in the present study, which is denoted as DPL. The dosage of cinnamon volatile oil(CVO), the model drug, was selected with viscosity, softening point and cohesion as evaluation indexes. The interaction between DPL and HMPSA was investigated by Fourier transform infrared spectroscopy(FT-IR) and differential scanning calorimetry(DSC). The compatibility of HMPSA with CVO and its transdermal ability were studied by in vitro transdermal test, adhesion, scanning electron microscopy( SEM) and rheological evaluation. The results showed that 5% CVO began to damage the structure of HMPSA. The initial adhesion and holding adhesion of DPL-modified HMPSA(DPL-HMPSA) were not significantly changed compared with those of HMPSA, whereas the 180° peel strength was decreased. FI-IR unraveled that DPL formed the n-π conjugated system with styrene-isoprene-styrene block copolymer(SIS), and there was no significant difference in the glass transition temperature according to DSC results, which indicated the good compatibility of DPL with HMPSA. With 5% CVO loaded, the drug content of DPL-HMPSA was 1. 14 times higher than that of HMPSA, and the decrease rate of drug content in DPL-HMPSA was 16% lower than that in HMPSA after 3 months. SEM demonstrated that CVO did not cause obvious structural damage to DPL-HMPSA. Rheological evaluation revealed that the storage modulus and loss factor of DPL-HMPSA were higher than those of HMPSA, and the cohesion was also stronger. The percutaneous penetration rate of cinnamaldehyde in DPL-HMPSA was 2. 25 times that of HMPSA. In conclusion, DPL-HMPSA had more stable structure, better compatibility with CVO, and higher in vitro transdermal efficiency of cinnamaldehyde than before the modification. This study can provide reference for the mitigation of the matrix structure damage caused by volatile oil components in TCM plasters and the enhancement of the content and in vitro transdermal rate of drug.
Adhesives ; Administration, Cutaneous ; Cinnamomum zeylanicum ; Oils, Volatile ; Spectroscopy, Fourier Transform Infrared

Objective To study the mechanism of right ventricular pulmonary artery coupling by fitting the pressure volume loop of pulmonary arterial hypertension patients and calculating the related parameters.Methods During January of 2015 to December of 2015,34 patients with pulmonary hypertension and 5 patients with patent oval foramen(PFO)were admitted in Wuhan Asian Heart Hospital,. Inclusion criteria for the pulmonary hypertension group were in accordance with the newest European guidelines for pulmonary hypertension . All of the patients were conducted invasive pressure catheter intervention and MRI. All the pressure data were digitized by GetData software and the CMR tools3D was used to derive right ventricular volume data, fitting the pressure volume loop and calculate the Pmax, Ees, Ea and other related parameters. 5 patients with PFO and 34 patients with pulmonary hypertension were divided into three groupswhich included:the control group (i.e. the patients with PFO), patients with pulmonary artery mean pressure less than 50 mmHg as group A and pulmonary artery mean pressure greater than or equal to 50 mmHg as group B. The pressure volume loop of the three groups were compared and the related parameters were calculated.Results The right ventricular Pmax were(53.05±12.87) mmHg, (134.73±26.38) mmHg, (207.88±65.67) mmHg, in the control group, group A and B respectively. There were significant differences when compared among the 3 groups. There was no statistical difference in Ees between the control group and group A(P>0.05). The Ees of group B was significantly higher than the control group[(1.53±0.97)vs.(0.60±0.28),P<0.05]. The Ea of group B was higher than the control[(1.34±0.74) vs.(0.39±0.15),P<0.05]. The overall ratio of Ees/Ea was lower in group B as compared to the control group [(1.12±0.47)vs.(1.62±0.51),P<0.05].Conclusions In the early stage of pulmonary hypertension, right ventricular contractility preserves and can overcome the slightly elevated afterload .The right ventricle and pulmonary artery coupled with good work. With the increasing mean pulmonary artery,the afterload of right ventricular increases and right ventricular contractility needs further increase to fight against the elevated afterload. The elevation of contractility cannot overcome the change of afterload, resulting in the off paired of mechanical efflciency, causing the right ventricle- pulmonary artery coupling decreases.

Objective To evaluate the safety and efficacy of the CARTO3-based total three-dimensional(T3D,total three-dimensional)zero X-ray mapping technique in radiofrequency catheter ablation of elderly patients with atrial fibrillation. Methods A total of 60 patients diagnosed with paroxysmal atrial fibrillation underwent radiofrequency catheter ablation at the Beijing Anzhen Hospital Arrhythmia Center from December 2015 to April 2017 were included. All patients were randomly divided into the study group(30 cases) and the control group(30 cases). T3D technique was utilized in the study group, and patients in the control group received conventional AF ablation. The procedure parameters success rate of circumferential pulmonary vein isolation(CPVI), rates of atrial fibrillation recurrence complication were compared between the two groups. Results All the 60 patients with paroxysmal atrial fibrillation had successful atrial fibrillation ablation and finished follow-up. Compared with the control group, the time of atrium three-dimensional reconstruction in the study group was longer [study group vs control group:(57.7±11.0)min vs.(10.4±3.5)min,P<0.001)];X-ray exposure time was significantly shorter in the study group[study group vs control group:0 min vs.(15.73±3.91)min,(P<0.001)]. The diff erence in circumferential pulmonary vein ablation time between the two groups was not of statistical significance[study group vs. control group:(49.9 ± 11.3)min vs.(51.1 ± 12.6)min,P=0.699].CPVI was successful in all patients in both groups. There was no signifi cant diff erence in the early and late recurrence rate and the incidence of complications between the two groups(P>0.05). Conclusions The application of T3D technique in radiofrequency ablation for elderly patients with paroxysmal atrial fi brillation is safe and eff ective, which can reduce the time of X-ray exposure and has important clinical value.

Objective To investigate the employers' and employees' satisfaction of Zhejiang Province on occupation health examination and diagnosis of occupational diseases, and to guide and to standardize the occupation health examination and occupational disease diagnosis. Methods A random sample of 953 employers, 1791 workers with health examination and 135 workers with diagnosis of occupational diseases were selected in the survey, and the questionnaire about the Satisfuction on occupation health examination and occupation disease diagnosis were used in this survey. Results A total of 2879 questionnaires were sent out, in which 2841 valid questionnaires were returned, and the effective recovery rate was 98.68%. The recognition rates on comfortable environment, clear instructions process, workflow notification, and attention notification were all above 98%. The satisfaction rates for all items were above 86%, and the total satisfaction rate was 89.27% . The total satisfaction rates of workers with health examination, workers with diagnosis of occupational diseases and employers were 89.28%, 82.03%, and 90.22%, respectively. The recognition rates on clear instructions process and attention notification, and the satisfaction rates on service attitude, result information and overall satisfaction were significantly different between different types of respondents (P<0.05) . The results of pair wise comparison showed that the satisfaction rates of workers with diseases diagnosis on service attitude, results information and overall satisfaction were significantly lower than those of employers (P<0.05) . The overall satisfaction rate of workers with diagnosis of occupational diseases was lower than that of workers with health examination (P=0.011) . The recognition rates of workers with health examination on clear instructions process and attentions notification were lower than those of employers (P<0.016) . There was a significant difference in the overall satisfaction between respondents in different regions (P<0.01) . Conclusion The service of occupational health examination and occupational disease diagnosis services should be further improved. We should better learn the demands of employees and employers, improve service attitude, optimize service processes, shorten service time, and improve service quality and satisfaction.