[Analysis and considerations on revision of instructions for traditional Chinese medicine injections].

According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.

[Composition analysis,antioxidative and antibacterial activities comparison of agarwood oils extracted by supercritical and steam distillation].

Agarwood is a traditional and precious medicinal material and natural spice in China and other southeast Asian countries.As the head of all spices,agarwood has many pharmacological activities such as analgesia,antidiarrheal,anti-inflammatory and antibacterial effects. Due to its high price and scarce resources,there were just a few previous studies on it,mainly focusing on the chemical compositions of the agarwood essential oil and solvent extract mixture. The components of agarwood oils obtained by supercritical extraction and steam distillation were analyzed by using Gas Chromatography-Mass Spectrometer( GC-MS),and then the agarwood oils compositions and contents were compared between the traditional extraction method and the recently emerging supercritical extraction method. Antioxidant experiments of scavenging DPPH,ABTS,hydroxyl radical,total reducing power and MIC experiments of five kinds of tester strains such as staphylococcus aureus were combined to illustrate the differences between these two kinds of agarwood oils in terms of antioxidant and bacteriostatic activities. The results showed that the main components of agarwood oil were sesquiterpenoids( 68. 68%) in steam distillation extraction method,but sesquiterpenoids( 23. 78%) and chromones( 29. 42%) in supercritical extraction method. Fourteen common components included benzyl acetone,α-santalol,γ-eudesmol,agarospirol and guaiol etc. The antioxidant activity and inhibitory MIC of agarwood oils in supercritical extraction method were better than those in steam distillation method,and the inhibitory effect of agarwood oil on the growth of bacillus subtilis was found for the first time.

Design, synthesis and antitumor activity of steroidal pyridine derivatives based on molecular docking.

With steroid as a carrier nucleus and introducing a pyridine heterocycle as a pharmacophore on the D ring, a series of steroidal pyridine derivatives were designed and studied for their antitumor activity by molecular docking software. The compounds were synthesized as small molecule inhibitors and studied as anticancer agents. The synthesis of the analogs was performed in a one-pot multi-component reaction and the corresponding compounds were screened in vitro for their antitumor activity. Four adherently growing cancer cell lines were used and arranged before dosing. Among all compounds screened for their antitumor activity, compounds 2f and 2p were found to be the most active. Here, the most obvious changes in the morphology of the treated cells could be observed.

[Simultaneous determination of six triterpenoid acids from Guizhi Fuling capsules by UPLC-MS/MS].

To establish a UPLC-MS/MS method for simultaneous determination of six triterpenoid constituents (pachymic acid, dehydropachymic acid, dehydrotumulosic acid, polyporenic acid C, dehydroeburicoic acid and dehydrotra metenolic acid) in Guizhi Fuling capsules (GFC). Chromatographic analysis was conducted on Agilent Porosheell 120 SB-C18 column (4.6 mm×150 mm, 2.7 µm), with 0.1% formic acid aqueous solution-methanol as the mobile phase for gradient elution at a flow rate of 0.4 mL•min-1. The column temperature was 30 ℃ and the sample size was 5 µL. The samples were analyzed by tandem mass spectrometer with negative electrospray ionization (ESI) source, and monitored under a multiple reaction monitoring (MRM) mode, with the quantitative ion pairs m/z 527.8→465.5 (pachymic acid), m/z 525.6→465.6 (dehydropachymic acid), m/z 483.4→337.3 (dehydrotumulosic acid), m/z 481.5→419.5 (polyporenic acid C), m/z 467.4→337.1 (dehydroeburicoic acid), m/z 453.4→337.0 (dehydrotra metenolic acid). Six triterpenoid acids showed good linear relationships within the investigated concentration ranges (r> 0.996 8), with RSDs of precision less than 6.2%, and all RSDs of repeatability less than 5.9%. The average recovery rate was 97.90%, 100.2%, 99.60%, 101.7%, 102.6% and 103.0% respectively. The method was rapid, accurate, repeatable and could be used as a method for quantitative determination of triterpenoid acids in Chinese medicine prescriptions, providing a reference method for the quality control of Guizhi Fuling capsules and providing a reference for the content determination for Chinese medicine prescriptions containing Poria cocos.

[Application of molecularly imprinted technology for separation of PGG from Guizhi Fuling capsule].

1,2,3,4,6-penta-O-galloyl-D-glucose (PGG) is one of the main active compounds of Guizhi Fuling capsule. Molecularly imprinted polymers (MIP) have high affinity toward template molecules synthesized by molecularly imprinted technology for its specific combined sites, which can overcome the shortcoming of traditional separation methods, such as complex operation, low efficiency, using large quantity of solvent and environmental pollution. In this paper, surface molecularly imprinted polymer (SMIP) was prepared by surface imprinting with PGG as the template molecule. Its adsorption capacity was measured by the scatchard equation. The separation of PGG from Guizhi Fuling capsule at preparatived scale was achieved with molecularly imprinted polymer as stationary phase and the purity was 90.2% by HPLC. This method can be used to prepare PGG from Guizhi Fuling capsule with large capacity and is easy to operate. It provides a new method for efficient separation and purification for other natural products.

[Anti-complementary phenolic acids from Lonicera japonica].

OBJECTIVE: To study the anti-complementary phenolic acids from Lonicera japonica. METHOD: The anti-complementary activity-directed isolation was carried out with the hemolysis test as guide. All isolation was evaluated for their in vitro anti-complementary activities. The structures were identified by various spectroscopic data including ESI-MS, 1H-NMR, 13C-NMR data. RESULT: Fourteen compounds were isolated from the EtOAc fraction of L. japonica extracts, including 8 phenolic acids: 5-O-caffeoylquinic acid (1), chlorogenic (2), 4-O-caffeoylquinic acid (3), 3,5-di-O-caffeoylquinic acid (4), 4,5-di-O-caffeoylquinic acid (5), 3,4-di-O-caffeoylquinic acid (6), caffeic acid (7) and methyl caffeate acid (8); 3 iridoids: secologanoside (9), sweroside (10) and secoxyloganin (11); and 3 flavonoids: luteolin (12), quercetin (13) and kaempferol (14). Compounds 1-9 and 11-14 showed anti-complementary activity in different extents and 3,5-di-O-caffeoylquinic acid (4) exhibited the most significant activity against the classical pathway. CONCLUSION: Compound 14 is obtained from this plant for the first time, phenolic acids are the main anti-complementary constituents of L. japonica and 3,5-di-O-caffeoylquinic acid(4) is a potential complement inhibitor with strong activity, which worthy to be studied further in the future.

[Chemical constituents from Artemisia annua].

OBJECTIVE: To investigate the chemical constituents of dried whole plants of Artemisia annua. METHOD: The chemical constituents were isolated by repeated silica gel chromatography, medium pressure column chromatography, and semi-preparative HPLC, and their structures were elucidated by spectroscopic analyses and comparison of NMR data with those reported in literature. RESULT: 15 compounds were isolated and identified to be 5-O-[(E)-Caffeoyl] quinic acid(l), 1,3-di-O-caffeoylquinic acid(2), 4 5-di-O-caffeoylquinic acid(3), 3, 5-di-O-caffeoylquinic acid (4), 3, 4-di-O-caffeoylquinic acid (5), methyl-3,4-di-O-caffeoylquinic acid(6), methyl-3,5-di-O-caffeoylquinic acid(7), 3,6'-O-diferuloylsucrose(8), 5'-ß-D-glucopyranosyloxyjasmonic acid(9), Scopoletin(10), scoparone (11), 4-O-ß-D-glucopyranosyl-2-hydroxyl-6-methoxyacetophenone (12), chrysosplenol D (13), casticin (14), chrysosplenetin(15). CONCLUSION: Compounds 2, 6, 8 and 9 are obtained from the Artemisia genus for the first time. Compounds 7 and 15 are obtained from this plant for the first time.

[Application of case-based learning in clinical internship teaching of conservative dentistry and endodontics].

PURPOSE: To investigate the education effect of case-based learning (CBL) pattern on clinical internship of conservative dentistry and endodontics. METHODS: Forty-one undergraduates were randomly assigned into CBL group and traditional teaching group. After clinical internship in the department of conservative dentistry and endodontics for 11 weeks, each student in the 2 groups underwent comprehensive examinations including medical record writing, case analysis, academic knowledge, professional skills and the ability of winning the trust of the patients. The scores were compared between the 2 groups using SPSS 13.0 software package. RESULTS: There was no significant difference between the 2 groups with regard to the scores of academic knowledge and profession skills (P>0.05). However, the results of medical record writing, case analysis and the ability of winning the trust of the patients showed significant difference between the 2 groups(P<0.05). CONCLUSIONS: Proper application of CBL in clinical internship of conservative dentistry and endodontics contributes to improve students' ability of clinical thinking, synthetical analysis and adaptability to different patients.

Speciosaperoxide, a new triterpene acid, and other terpenoids from Chaenomeles speciosa.

Investigation on the EtOH extract of the fruits of Chaenomeles speciosa led to the isolation of a new triterpene acid bearing an unusual hydroperoxyl substitute group at C-11, speciosaperoxide (1), along with six known triterpenoids, 3beta-acetoxyurs-11-en-13beta,28-olide (2), 3-O-acetyl ursolic acid (3), oleanolic acid (4), ursolic acid (5), masilinic acid (6), and tormentic acid (7), and three known norsesquiterpenoids, roseoside (8), vomifoliol (9) and (6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-[beta-d-xylopyranosyl (1 --> 6)-glucopyranoside] (10). Their structures were elucidated on the basis of spectroscopic data and comparison with reference data. Besides compound 1, compounds 2, 8-10 were obtained from this genus for the first time. None of these compounds exhibited inhibitory activity against T-and B-lymphocyte proliferation.

[Clinicopathologic analysis and genetic investigation of two families with cherubism].

OBJECTIVE: To study genetic feature, clinical and histopathological characteristic of two Chinese kindreds with cherubism (CBM). METHODS: Two Chinese kindreds with CBM were investigated. The affected individuals of two families were analyzed with medical history, clinical manifestations, classified grading system, radiographic assessment, histopathological findings, and hereditary nature. RESULTS: There were 2 individuals affected with CBM in family A and 3 patients involving three generations in family B. Two probands were diagnosed aggressive form cherubism and classified as grade IV. In histopathological findings, besides varying numbers of multinucleated giant cells in a stroma of fibroblasts and the eosinophilic cuffing surrounding some vessels, actively proliferating areas with clear mitoschisis and relative dormant areas with loose fibrous tissue and bone were also presented in microscopic fields of the lesion. CONCLUSIONS: Cherubism is caused by autosomal dominant inheritance. The diagnosis should be based on the genetic, clinical, radiological, and pathological aspects of the disease.

Germline mutations of the PTCH gene in families with odontogenic keratocysts and nevoid basal cell carcinoma syndrome.

BACKGROUND/AIMS: Odontogenic keratocysts (OKC) are aggressive lesions in the jaws, which can occur as isolated cases or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations on PTCH gene have been identified in patients with NBCCS. It was hypothesized that PTCH mutations may be causative in isolated OKC. This study aims to investigate germline mutations of PTCH in families with OKC and NBCCS. METHODS: Three Chinese families with OKC and NBCCS were enrolled in the study. The diagnosis was based on examination and medical history. Mutation analysis was performed by amplifying all exons of PTCH and sequencing the products. RESULTS: One family with isolated OKC (family 1) and the other two families with NBCCS were diagnosed. Three novel germline mutations in PTCH were identified, including a missense mutation (p.S1089 > P) in family 1, a nonsense mutation (p.Q160X) in family 2 and a de novo mutation (c.768_777delGACAAACTTC) in family 3. CONCLUSIONS: It is proposed that isolated OKC can be inherited in an autosomal dominant mode. The results suggest that germline mutations on PTCH can cause isolated OKC, and that the PTCH gene responsible for NBCCS plays an important role in the formation of OKCs even when they are not syndrome-related.

Cleaning effectiveness and shaping ability of rotary ProTaper compared with rotary GT and manual K-Flexofile.

PURPOSE: To compare the cleaning efficacy and shaping ability of engine-driven ProTaper and GT files, and manual preparation using K-Flexofile instruments in curved root canals of extracted human teeth. METHODS: 45 canals of maxillary and mandibular molars with curvatures between 25 degrees and 40 degrees were divided into three groups. The groups were balanced with regard to the angle and the radius of canal curvature. Canals in each group were prepared to an apical size of 25 with either the rotary ProTaper or GT system, or manually with K-Flexofile using the modified double-flared technique. Irrigation was done with 2 mL 2.5% NaOCl after each instrument and, as the final rinse, 10 mL 2.5% NaOCl then 10 mL 17% EDTA and finally 5 mL distilled water. The double-exposure radiographic technique was used to examine for the presence of apical transportation. The time required to complete the preparation, as well as any change in working length after preparation were recorded. The roots were then grooved and split longitudinally. The amounts of debris and smear layer were evaluated at the apical, middle and coronal regions under the scanning electron microscope. Data were analyzed either parametrically with the F-test or non-parametrically using the Kruskal-Wallis test, where appropriate. RESULTS: Two GT files but none of the K-Flexofile and ProTaper instruments separated. For debris removal, the ProTaper group achieved a better result than GT (P < 0.05) but not the K-Flexofile group at all three regions (apical, middle and coronal). K-Flexofiles produced significantly less smear layer than ProTaper and GT files only in the middle third of the canal (P < 0.01). Both NiTi rotary instruments maintained the original canal shape better than the K-Flexofiles (P < 0.05) and required significantly less time to complete the preparation.