OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To explore the diagnostic value of total bilirubin to albumin ratio(B/A ratio)combined with alpha-fetoprotein(AFP)and abnormal prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)for hepatocellular carcinoma(HCC).Methods:35 HCC patients(HCC group),35 cirrhosis patients(cirrhosis group),35 HCC patients post-transcatheter arterial chemoembolization(TACE)(TACE postoperative group),and 35 healthy volunteers(healthy control group)were selected in our hospital from October 2023 to October 2024.The serum B/A ratio,AFP,and PIVKA-Ⅱ levles were measured and compared across the groups.The correlations between serum B/A ratio,AFP,and PIVKA-Ⅱ in the HCC group were analyzed.The B/A ratio,AFP,PIVKA-Ⅱ were compared across different clinical and pathological features in HCC patients.The serum B/A ratio,AFP,and PIVKA-Ⅱ levels were compared pre and post operation in the HCC group.The diagnostic value of B/A ratio,AFP,PIVKA-Ⅱ alone and in combination for HCC were analyzed by receiver operating characteristic(ROC)curves.Results:The serum B/A ratio,AFP,and PIVKA-Ⅱ levels in HCC group and TACE postoperative group were significantly higher than those in the cirrhosis group and healthy control group,and the HCC group was higher than that in the TACE postoperative group(P＜0.05).Pearson correlation analysis results showed that,B/A ratio in the HCC group was positively correlated with AFP(r=0.352,P=0.001),B/A ratio was positively correlated with PIVKA-Ⅱ(r=0.327,P=0.003),and AFP was positively correlated with PIVKA-Ⅱ(r=0.285,P=0.008).Higher TNM stage,larger tumor diameter,presence of vascular invasion,and lower differentiation degree of HCC patients,who had higher B/A ratio,AFP,and PIVKA-Ⅱ levels(P＜0.05).Serum B/A ratio,AFP,and PIVKA-Ⅱ levels in the HCC group post operation were significantly lower than those in pre operation(P＜0.05).ROC curve analysis results showed that,when B/A ratio,AFP,and PIVKA-Ⅱ were detected separately,the area under the curve(AUC)was 0.785,0.756,and 0.802,respectively.The AUC for joint detection was 0.925.The AUC in combination was greater than that of individual detection of each indicator.Conclusion:The combination of B/A ratio,AFP,and PIVKA-Ⅱ testing significantly improves the diagnostic efficiency for HCC,which is worthy of clinical application.

Objective:To explore the diagnostic value of total bilirubin to albumin ratio(B/A ratio)combined with alpha-fetoprotein(AFP)and abnormal prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)for hepatocellular carcinoma(HCC).Methods:35 HCC patients(HCC group),35 cirrhosis patients(cirrhosis group),35 HCC patients post-transcatheter arterial chemoembolization(TACE)(TACE postoperative group),and 35 healthy volunteers(healthy control group)were selected in our hospital from October 2023 to October 2024.The serum B/A ratio,AFP,and PIVKA-Ⅱ levles were measured and compared across the groups.The correlations between serum B/A ratio,AFP,and PIVKA-Ⅱ in the HCC group were analyzed.The B/A ratio,AFP,PIVKA-Ⅱ were compared across different clinical and pathological features in HCC patients.The serum B/A ratio,AFP,and PIVKA-Ⅱ levels were compared pre and post operation in the HCC group.The diagnostic value of B/A ratio,AFP,PIVKA-Ⅱ alone and in combination for HCC were analyzed by receiver operating characteristic(ROC)curves.Results:The serum B/A ratio,AFP,and PIVKA-Ⅱ levels in HCC group and TACE postoperative group were significantly higher than those in the cirrhosis group and healthy control group,and the HCC group was higher than that in the TACE postoperative group(P＜0.05).Pearson correlation analysis results showed that,B/A ratio in the HCC group was positively correlated with AFP(r=0.352,P=0.001),B/A ratio was positively correlated with PIVKA-Ⅱ(r=0.327,P=0.003),and AFP was positively correlated with PIVKA-Ⅱ(r=0.285,P=0.008).Higher TNM stage,larger tumor diameter,presence of vascular invasion,and lower differentiation degree of HCC patients,who had higher B/A ratio,AFP,and PIVKA-Ⅱ levels(P＜0.05).Serum B/A ratio,AFP,and PIVKA-Ⅱ levels in the HCC group post operation were significantly lower than those in pre operation(P＜0.05).ROC curve analysis results showed that,when B/A ratio,AFP,and PIVKA-Ⅱ were detected separately,the area under the curve(AUC)was 0.785,0.756,and 0.802,respectively.The AUC for joint detection was 0.925.The AUC in combination was greater than that of individual detection of each indicator.Conclusion:The combination of B/A ratio,AFP,and PIVKA-Ⅱ testing significantly improves the diagnostic efficiency for HCC,which is worthy of clinical application.

AIM To study the chemical constituents from the root tubers of Stephania kwangsiensis H.S.Lo and their tyrosinase inhibition and insecticidal activities.METHODS The 70％ ethanol extract from root tubers of S.kwangsiensis was isolated and purified by Sephadex LH-20,MCI,ODS,semi-prepative HPLC and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The tyrosinase inhibitory activities were determined by using levodopa as substrate,and the insecticidal activities were evaluated by the control effect of Diaphorina citri.RESULTS Twelve compounds were isolated and identified as tetrahydropalmatine ( 1 ),dehydrocrebanine ( 2 ),crebanine ( 3 ),stephanine ( 4 ),liriodenine ( 5 ),piperumbellactam A ( 6 ),sinoacutine ( 7 ),(+)-salutaridine N-oxide ( 8 ),bisnorargemonine ( 9 ),(+)-corytuberine (10),sebiferine (11) and palmatrubine (12).The IC50 values of compounds 5-7 to tyrosinase were (0.1702±0.0101),(0.7663±0.0331) and (0.5193±0.0075) mg/mL,respectively.The control effects of compounds 2-5,7,8,10-12 against D.citri ranged from ( 19.33±0.57 )％ to ( 77.15±0.45 )％.CONCLUSION Compounds 2,5,6,and 8-12 are isolated from this plant for the first time,6 and 9 are first obtained from genus Stephania.Compounds 5-7 displayed significant tyrosinase inhibition activities.Compounds 7,8 and 10 show strong insecticidal activities.

AIM To study the chemical constituents from the root tubers of Stephania kwangsiensis H.S.Lo and their tyrosinase inhibition and insecticidal activities.METHODS The 70％ ethanol extract from root tubers of S.kwangsiensis was isolated and purified by Sephadex LH-20,MCI,ODS,semi-prepative HPLC and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The tyrosinase inhibitory activities were determined by using levodopa as substrate,and the insecticidal activities were evaluated by the control effect of Diaphorina citri.RESULTS Twelve compounds were isolated and identified as tetrahydropalmatine ( 1 ),dehydrocrebanine ( 2 ),crebanine ( 3 ),stephanine ( 4 ),liriodenine ( 5 ),piperumbellactam A ( 6 ),sinoacutine ( 7 ),(+)-salutaridine N-oxide ( 8 ),bisnorargemonine ( 9 ),(+)-corytuberine (10),sebiferine (11) and palmatrubine (12).The IC50 values of compounds 5-7 to tyrosinase were (0.1702±0.0101),(0.7663±0.0331) and (0.5193±0.0075) mg/mL,respectively.The control effects of compounds 2-5,7,8,10-12 against D.citri ranged from ( 19.33±0.57 )％ to ( 77.15±0.45 )％.CONCLUSION Compounds 2,5,6,and 8-12 are isolated from this plant for the first time,6 and 9 are first obtained from genus Stephania.Compounds 5-7 displayed significant tyrosinase inhibition activities.Compounds 7,8 and 10 show strong insecticidal activities.

Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

ObjectiveTo establish an integrated method of fingerprint qualitative， multi-component quantitative analysis and chemometrics， and to evaluate the quality attributes and differences of Aurantii Fructus from different production areas and origins. MethodAnalysis was performed on COSMOSIL 5C₁₈-MS-Ⅱ column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile-0.2% phosphoric acid solution for gradient elution （0-4 min， 19%A； 4-5 min， 19%-21%A； 5-18 min， 21%A； 18-19 min， 21%-28%A； 19-27 min， 28%A； 27-28 min， 28%-40%A； 28-36 min， 40%A； 36-37 min， 40%-50%A； 37-42 min， 50%-60%A； 42-46 min， 60%-95%A； 46-55 min， 95%-100%A）， the flow rate was 1 mL·min^-1， the column temperature was 30 ℃， the detection wavelength was set at 320 nm， and the injection volume was 10 μL. High performance liquid chromatography （HPLC） fingerprints of Aurantii Fructus from different production areas and origins were established. Then， the quality of 26 batches of samples was evaluated by cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA）. A method for the determination of 12 components was developed and verified， and a thermal map-based CA of Aurantii Fructus from different production areas and origins was carried out based on the content difference of samples. ResultThe fingerprint and determination methods were well verified. The similarity of HPLC fingerprint of 12 batches of Aurantii Fructus was 0.85-0.996， 20 common peaks were calibrated and 14 of them were assigned. The resolution and linear relationship of 12 components in quantitative analysis were good. The recovery rates were 99.2%-101.0% with RSD≤2.0%. The results of CA， PCA and OPLS-DA indicated that the differentiation of Aurantii Fructus in different production areas was great， and there were differences among different cultivars. ConclusionThe qualitative analysis of fingerprint and quantitative analysis of multiple indexes based on the same chromatographic analysis conditions are convenient， accurate and reliable， and combined with chemometrics， the identification and quality analysis of Aurantii Fructus from different production areas and origins can be realized， which can provide reference for quality control and evaluation of Aurantii Fructus.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Aurantii Fructus is a commonly used qi-regulating medicinal herb in China. Both traditional Chinese medicine theory and modern experimental research demonstrate that Aurantii Fructus has dryness effect, the material basis of which remains unclear. In recent years, spectrum-effect relationship has been widely employed in the study of active ingredients in Chinese medicinal herbs, the research ideas and methods of which have been constantly improved. Based on the idea of spectrum-effect study, the ultra-high perfor-mance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) fingerprints of different fractions of Aurantii Fructus extract were established for the identification of total components. Then, the dryness effects of the fractions on normal mice and gastrointestinal motility disorder(GMD) rats were systematically compared. Finally, principal component analysis(PCA), Pearson bivariate correlation analysis and orthogonal partial least squares analysis(OPLS) were integrated to identify the dryness components of Aurantii Fructusextract. The results showed that narirutin, naringin, naringenin, poncirin, oxypeucedanin, and eriodictyol-7-O-glucoside had significant correlations with and contributed to the expression of AQP2 in kidney, AQP3 in colon, and AQP5 in submandibular gland, which were the main dryness components in Aurantii Fructus.
Animals ; Aquaporin 2 ; Chromatography, High Pressure Liquid ; Citrus ; Drugs, Chinese Herbal ; Gastrointestinal Motility ; Medicine, Chinese Traditional ; Mice ; Rats