The interaction of several small-molecule alkaloids,namely coptisine,jateorhizine,epiberberine,berberrubine,columbamine,fangchinoline and tetrandrine,with guanine-guanine-adenine(GGA)triplex DNA was investigated by mass spectrometry(MS),ultraviolet-visible(UV-vis)spectroscopy,fluorescence spectroscopy,and circular dichroism(CD)spectroscopy.The effect of the 7 kinds of metal ions on the stability of GGA triplex DNA was investigated by direct infusion electrospray ionization mass spectrometry(ESI-MS),and the binding degree was highest when Ni2+was employed.Among the 7 kinds of alkaloids,tetrandrine had the highest affinity to the GGA triplex.All the data unequivocally accommodated diverse mechanisms for interaction between the isoquinoline alkaloids and the GGA DNA triplexes.At least,electrostatic attraction and intercalative-binding modes were observed in the study.Interestingly,UV melting denaturation assay revealed that the two isoquinoline alkaloids including columbamine and berberrubine enhanced the stability of the GGA triplex structure.The UV-melting curve profile could not accurately determine the stabilizing effect of small molecules on the structure of GGA triplex DNA.Further detection by UV-vis spectroscopy showed that epiberberine could stabilize the structure of GGA triplex DNA,but other small molecules couldn't stabilize the structure of GGA triplex DNA.The mode of interaction was further investigated,and firstly,fluorescence spectroscopy was applied to construct the ethidium bromide(EB)-GGA triplex DNA system,and then the reactions of small molecule alkaloids at different concentrations with EB-GGA triplex DNA system were studied.And it was found that epiberberine,fangchinoline and tetrandrine small molecules could replace the EB and insert to bind GGA triplex DNA.Finally,the circular dichroism spectroscopy was used to investigate the binding mode,and the negative CD signal was found.The investigation provided new insights into the interaction of isoquinoline alkaloids with GGA triplex DNA.

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.

In this paper， through consulting relevant records in materia medica， medical and prescription books， and combining with modern literature， the name， origin， producing area， collection and processing of Gentianae Macrophyllae Radix in famous classical formulas from The Catalogue of Ancient Famous Classical Formulas （The First Batch） was systematically sorted out and textual research was carried out， in order to provide a basis for the development of the famous classical formulas containing Gentianae macrophyllae Radix. After textual research， it was found that Gentianae Macrophyllae Radix was the rectification of name in the past dynasties. In addition， there were other names such as Qinjiao， Qingua and Qinzhua. Gentiana macrophylla， G. straminea， G. dahurica and G. siphonantha were the main origin of this herb in ancient literature. Among them， G. macrophylla is the mainstream. In the Southern and Northern dynasties， G. straminea and G. macrophylla produced in northern Sichuan were recommended as the best. In the early Tang dynasty， G. macrophylla from the Liupan Mountain area at the border of Shanxi and Gansu provinces was the mainstream. During the Northern Song dynasty， G. siphonantha from Linxia and Qilian Mountain of Gansu province and G. macrophylla from eastern Shaanxi province were two new producing areas. In the Ming and Qing dynasties， the abundant base and production areas of Gentianae Macrophyllae Radix were gradually formed. In the past dynasties， harvesting was carried out in spring and autumn， and stored mainly by aeration drying or shade drying treatment. The processing methods are mainly the raw products after the net selection， cutting and drying， in addition to the frying， processing with wine and milk. G. macrophylla is recommended as the first choice for the herbal medicine involved in the famous classical formulas. Among them， wild products produced in Gansu and Shaanxi are the best， and raw products are recommended to be used. At the same time， it is suggested that G. siphonantha should be added to the subsequent edition of Chinese Pharmacopoeia as one of origins of Gentianae Macrophyllae Radix.

By consulting ancient herbal medicines and medical books， combined with modern documents and field investigations， the textual research of Pheretima has been conducted to verify the name， origin， producing area， quality， harvesting and processing changes， and sort out the relationship of origin between ancient and modern times， so as to provide reference and basis for the development and utilization of the related famous classical formulas. Through textual research， it is known that there are many aliases for Pheretima， the rectification of name was "Qiuyin" or "Baijing Qiuyin" in materia medica books. In the Song dynasty and later prescription books， the prescription name is mostly Dilong. From the beginning of Yaowu Chuchanbian （《药物出产辨》）， Dilong was used as the rectification of name. It is widely distributed in our country， which is produced all over the country and mostly wild. According to ancient Pheretima with "Baijing Dilong"， "Jingbai Shenzi" and "Datiao" as the principles of medicine， combined with historical origin， producing area and easy access， it is confirmed that Pheretima used in ancient times to the present is mainly Pheretima aspergillum， and it also has many other Qiuyin as Pheretima for medicinal purposes. Chinese Pharmacopoeia has unified the origin of the Pheretima since the 1995 edition based on historical origins and actual harvesting conditions. The medicinal material processed by P. aspergillum was called Guangdilong， and the medicinal materials processed by P. vulgaris， P. guillelmi and P. pectinifera were called Hudilong. Since then， all the herbal books published in the future are in line with Chinese Pharmacopoeia that was implemented at that time. The authentic production areas of Guangdilong are Guangdong and Guangxi， and the authentic production areas of Hudilong is Jiangsu， Shanghai， Zhejiang and Anhui. The Guangdilong produced in Guangdong and Guangxi has the best quality. After harvesting， remove the soil and offal， wash and dry. Clinically cut into sections for medicine， or prepare medicine according to prescription. The Pheretima in ancient used "Baijing Dilong"， "Jingbai Shenzi" and "Datiao" as the mainstream quality evaluation standards. According to historical origins， P. aspergillum should be the main source of Pheretima， and its quality is better than other species. Therefore， it is recommended that Pheretima in Shentong Zhuyutang use P. aspergillum， which is produced in Guangdong， Guangxi and other places. After harvest， the abdomen was opened in time to remove the viscera and sediment， washed and dried.

By consulting ancient Chinese herbal medicines and medical books， combined with modern documents， the textual research of Polygonati Rhizoma has been conducted to verify the name， origin， bitter-flavored Polygonatum species， Latin name evolution， origin， quality evaluation， harvesting and processing changes， so as to provide reference and basis for the development and utilization of the famous classical formulas. Through textual research， it can be seen that there are many other names for Polygonati Rhizoma， and Huangjing is the correct name since Mingyi Bielu. Based on the original research， it is concluded that P. sibiricum and P. cyrtonema were the mainstream of Polygonati Rhizoma before the Tang dynasty， and P. kingianum was added in the Qing dynasty. According to the shape of medicinal materials， these Polygonatum species were called Jitou Huangjing， Jiangxing Huangjing and Dahuangjing. The harvest time of Polygonati Rhizoma is spring and autumn. After harvest， it is steamed and dried in the sun， and its processing method is mainly "nine steaming and nine storms". Bitter-flavored Polygonatum is mainly P. cirrhifolium， P. zanlanscianense， P. curvistylum and P. verticillatum， which are not suitable for medicine. Based on textual research， it is recommended that when developing famous classical formulas and health products with Polygonati Rhizoma as the main raw material， the origin and producing area should be clear and fixed， and P. sibiricum or P. cyrtonema with clear origin should be used. It is necessary to conduct germplasm survey and sampling in the producing area， establish a planting base and a traceability system for Polygonati Rhizoma， in order to control the quality and stabilize the efficacy of the products. The processing method of Polygonati Rhizoma can be determined according to the product function positioning.

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

The present study aimed to regulate the market circulation of Caryophylli Flos and formulate standards for commodity specifications and grades of Caryophylli Flos. Market survey was carried out in four major medicinal material markets with 48 samples of Caryophylli Flos collected. The property, 100-seed weight, impurity percentage, moisture, and eugenol content in Caryophylli Flos of different specifications from different producing areas were determined and analyzed. The results showed that 27.1% of the samples surveyed on the markets did not meet the requirements of Chinese Pharmacopoeia(2020 edition). The 100-seed weight and the property are important factors for the classification of Caryophylli Flos specifications. There were significant differences in the property, 100-seed weight, impurity percentage, and eugenol content in Caryophylli Flos samples of different specifications from different producing areas, and also differences in the proportions of different specifications in Caryophylli Flos samples from different producing areas. The African-originated Xiaohong(medium grade) and Guangxi-originated Xiaohong(medium grade) accounted for 70% and 66.7% respectively, the Indonesian-originated Dahong(top grade) for 56.2%. In conclusion, there are many problems in the circulation of Caryophylli Flos at present, mainly including the loss of origin information, no standards for specifications, non-implementation of grade standards, excessive impurities, and no evidence for authenticity identification. According to the classification of Caryophylli Flos specifications in this study, the average eugenol content of Xiaohong is significantly higher than the Dahong by 4.74%.
China ; Drugs, Chinese Herbal/analysis* ; Indonesia

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n=123), ASP under X-ray alone (X-ray group, n=118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA₂DS₂-VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% (n=138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% (n=135), and the ratio of repeat ablation was 17.8% (n=43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P=0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P<0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P<0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P=0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P=0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.
Adult ; Aged ; Atrial Fibrillation/surgery* ; Catheter Ablation ; Feasibility Studies ; Heart Septal Defects, Atrial ; Humans ; Male ; Middle Aged ; Punctures ; Radiofrequency Ablation ; Stroke Volume ; Ventricular Function, Left

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

OBJECTIVESTo analyze the survival outcomes of the surgery for colorectal cancer with liver metastases (CRCLM), and study the mode of multi-disciplinary team (MDT) for CRCLM.

METHODSThe retrospective analysis was conducted for 38 patients with CRCLM received MDT management and surgical treatment from January 2009 to August 2011. The peri-operative and survival outcomes of MDT and surgery were evaluated.

RESULTSAll the cases met the present criteria of resetability for CRCLM, but only 4 cases (10.5%) met the previous one. Coloproctectomy and hepatectomy were performed in all cases, with 39 colorectal neoplasms and 155 liver lesions removed. One case died of postoperative septic shock. Colorectal and hepatic specific complications were absent in the others patients except one case of biliary leak which was treated with conservative management. Neoadjuvant chemotherapy was arranged in 13 cases. Adjuvant chemotherapy was administered for every patient. After a mean follow-up of (22 ± 10) months according to the finding time of liver metastases, recurrence and metastases were observed in 16 cases and 6 cases died of late-stage cachexia. The 1-, 2- and 3-overall survival rate were 94.4%, 85.3% and 75.8% respectively, and the 1-, 2- and 3-disease-free survival rate were 70.1%, 54.2% and 54.2% respectively.

CONCLUSIONSMDT mode for resectable CRCLM is recommendable. Surgical resection of CRCLM is feasible and safe, which seems to achieve favourable short-middle oncologic outcomes. And long-term survival is expected.

Adult ; Aged ; Chemotherapy, Adjuvant ; Colorectal Neoplasms ; mortality ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; mortality ; secondary ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome