Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer / 中国中药杂志

Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.

Echocardiographic diagnosis of sinus of Valsalva aneurysm / 中山大学学报(医学科学版)

ObjectiveTo summarize the echocardiographic features of sinus of Valsalva aneurysm （SVA）， analyze the causes of missed diagnosis， thus explore the diagnostic skills and improve the diagnostic accuracy for SVA. MethodsThe echocardiographic features and clinical data of 52 SVA patients who underwent surgery in the First Affiliated Hospital of Sun Yat-sen University from January 2014 to March 2022 were retrospectively reviewed. The patients were divided into 5 types according to modified Sakakibara classification system. ResultsThere were 32 male and 20 female patients with their age of 18~66 （36.1±11.6） years. Of the 52 aneurysms， 44 originated from the right coronary sinus （RCS）， 8 from noncoronary sinus （NCS） and none from left coronary sinus （LCS）. Among the 35 SVAs protruding into the right ventricle， including type I， type Ⅱ and type Ⅲv， 32 （91.4%） were associated with ventricular septal defect （VSD）. There were 2 （17.6%） associated with VSD among the 17 SVAs protruding into the right atrium or other sites of the heart， including type Ⅲa， type Ⅳ and type Ⅴ. SVA was frequently associated with aortic valve disease， 27 cases （51.9%） of which needed surgical valve replacement or valvoplasty. SVA was missed in 4 patients and VSD in 8， with the misdiagnosis rates of 7.7% and 23.5%， respectively. The most commonly missed VSD diagnosis was subarterial VSD with type I SVA. Of the 19 SVAs associated with infective endocarditis （IE）， 2 were missed， with the misdiagnosis rate of 10.5%. ConclusionThe ultrasound images of SVA are diverse and complex. SVA protruding into the right atrium is rarely associated with VSD， while SVA protruding into the right ventricle is frequently associated with VSD. SVA is also prone to be associated with aortic valve disease and IE， which makes the diagnosis more challenging. Therefore， during ultrasound examination， we must vigilantly and flexibly make use of the multiple scan slices so as to decrease the rate of missed diagnosis and improve the diagnostic accuracy for SVA.

CRISPR/Cas9-mediated endogenous TCR knockout enhances TCR-T cells targeted killing HPV16-positive cervical cancer cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：基于CRISPR/Cas9基因编辑技术制备无内源TCR的TCR-T细胞并鉴定其在体外杀伤HPV16阳性宫颈癌SiHa细胞的功能。方法：培养健康志愿者外周血CD8+ T细胞和Jurkat细胞，CRISPR/Cas9基因编辑技术敲除CD8+ T、Jurkat细胞的TCR基因，制备过表达转基因TCR的重组慢病毒，在敲除内源性TCR的CD8+ T和Jurkat细胞中用慢病毒过表达转基因TCR制备TCR-T细胞，多色FCM检测TCR-T细胞中TCR和CD3的表达水平，荧光素酶活性实验检测TCR-T细胞对HPV16阳性SiHa细胞的杀伤效率。结果：CRIPSR/Cas9基因编辑技术高效地敲除了外周血CD8+ T细胞和Jurkat细胞中的TRAC和TRBC基因，敲除效率分别为（81.4±4.5）%、（98.5±0.07）%，制备的无内源TCR的TCR-T细胞高效表达转基因TCR，在外周血CD8+ T和Jurkat细胞中表达率为（66.0±17.8）%、（97.3±2.6）%，敲除内源TRAC和TRBC基因有效增强CD8+ T和Jurkat细胞膜表达转基因TCR（均P<0.01），敲除内源TCR增强TCR-T细胞特异性杀伤HPV16阳性的SiHa细胞[（71.4±1.0）% vs （35.1±2.0）%，P<0.01）]。结论：无内源TCR的TCR-T细胞显著增强转基因TCR的表达和对HPV16阳性宫颈癌SiHa细胞的靶向杀伤能力，为提高TCR-T细胞的临床疗效提供了实验依据。

Mechanism of Transcription Factor SP1 Regulates Expression of Tripartite Motif-containing Protein 7 in Hepatocellular Carcinoma / 中国生物化学与分子生物学报

Tripartite motif containing protein 7 (TRIM7), as a member of the E3 ubiquitin ligase TRIM family, plays an important regulatory role in immune regulation, metabolism and other physiological processes. The aberrant expression of TRIM7 is closely related to the development and progression of hepatocellular carcinoma (HCC) and it shows a complex regulatory role. However, the regulatory mechanism for the expression of TRIM7 in HCC remains unknown. In this study, multiple online databases were used to analyze the expression of TRIM7 in HCC and data indicated that TRIM7 expression was upregulated in HCC and correlated to poor prognosis. Subsequently, the transcription factor binding sites in the TRIM7 promoter region were analyzed using UCSC and JASPAR databases, and the results showed that TRIM7 promoter contains four SP1 binding sites. In this work, we demonstrated that SP1 could directly bind to its binding sites in TRIM7 promoter and positively regulate the transcriptional activity driven by the TRIM7 promoter using dual luciferase reporter experiments and the ChIP-PCR method. Moreover, our results also showed SP1 overexpression upregulated the expression of TRIM7 at both mRNA and protein levels (P<0. 01),and SP1 inhibitor, mithramycin A, could reverse the activated effect of SP1 on TRIM7 expression (P<0. 01). In conclusion, this study preliminarily reveals the regulatory mechanism of TRIM7 upregulation in HCC, which provides an important theoretical basis for further study of the gene function, early diagnosis and targeted therapy.

Mechanism of Chinese Herbal Monomers Against Cisplatin-induced Resistance of Ovarian Cancer： A Review / 中国实验方剂学杂志

Because the early symptoms of ovarian cancer are not typical and there is a lack of effective screening methods， most patients are diagnosed at an advanced stage， which seriously endangers the health of modern women. Platinum-based chemotherapy after tumor reduction is the first choice for patients with advanced and recurrent ovarian cancer， but almost all patients with recurrent ovarian cancer will eventually develop platinum resistance. Therefore， the search for natural， safe， and effective chemotherapeutic sensitizers has become an urgent and important topic in the study of ovarian cancer. With the increasingly extensive application of traditional Chinese medicine （TCM） in the treatment of cancer， the research on Chinese herbal monomers is also deepening， and the mechanisms of Chinese herbal monomers in intervening in cisplatin （DDP）-induced resistance of ovarian cancer is becoming increasingly clearer. Based on the research status of Chinese herbal monomers available in many Chinese and English databases， it was found that Chinese herbal monomers were involved in the reversal of DDP-induced resistance of ovarian cancer via many routes， mainly through increasing the intracellular drug concentration， reversing the blocked apoptosis， correcting the abnormal intracellular signaling pathway， enhancing DNA damage and inhibiting DNA repair， regulating intracellular autophagy， and suppressing epithelial mesenchymal transition （EMT）. Chinese herbal monomers weaken the resistance of ovarian cancer to DDP from multiple targets and enhance the toxicity of DDP to ovarian cancer cells in vitro and transplanted tumors in vivo. Therefore， Chinese herbal monomers are expected to become natural sensitizers for ovarian cancer chemotherapy with DDP. However， the current studies on Chinese herbal monomers are still confined to the single experimental type， and their action mechanisms and toxic and side effects remain to be further clarified. The application of Chinese herbal monomers for sensitizing DDP chemotherapy still needs to be verified by multi-target， multi-level experimental studies and large-scale clinical studies in the future.

Mechanisms of Guizhi Fulingwan Against Ovarian Cancer： A Review / 中国实验方剂学杂志

Ovarian cancer （OC） is one of the three major gynecological malignancies. Due to its insidious onset at the early stage，most of OC patients are diagnosed at the advanced stage， making it become one of the most deadly gynecological tumors and thus a hot topic in the field of gynecology and oncology. Guizhi Fulingwan is a classic Chinese herbal compound derived from Synopsis of Golden Chamber （《金匮要略》） for the treatment of abdominal mass in women on account of its efficacy in resolving stasis， generating new blood， and eliminating mass. The articles concerning the treatment of OC with Guizhi Fulingwan were searched from such databases as China National Knowledge Infrastructure （CNKI）， PubMed，Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP） and collated for expounding its action mechanisms， in order to provide ideas for further research on its pharmacological effects，clinical application， and promotion. Clinically，Guizhi Fulingwan has been proved to control the growth of myoma，correct serological indexes，enhance chemotherapy sensitivity and anti-tumor immunity，reduce postoperative recurrence rate， and improve the quality of life of patients. As revealed by experimental research，Guizhi Fulingwan alleviates the pathological state of animal and cell models by promoting mitochondrial apoptosis and tumor immunity，inhibiting vascular factors，inducing cell cycle arrest， and reversing multidrug resistance. Guizhi Fulingwan exerts a certain therapeutic effect on OC through multi-target and multi-channel mechanisms， reflecting the advantages of traditional Chinese medicine in treating OC.

Erianin Inhibits Proliferation of Bladder Cancer 5637 Cells Through Akt / 中国实验方剂学杂志

ObjectiveTo investigate the role of protein kinase B （Akt） overexpression in the inhibition of human bladder cancer 5637 cell proliferation by erianin and related mechanisms. MethodThe 5637 cells stably over-expressing Akt were induced using the lentivirus vector. The 5637 cells infected with the empty vector were classified into blank group. Then the Akt group， empty vector combined with erianin （62.5 μg·L-1） group， and Akt combined with erianin （62.5 μg·L-1） group were set up. The cell viability was detected by cell counting kit-8 （CCK-8） assay， and the clone formation of 5637 cells in each group was determined in the clone formation experiment. The cell cycle distribution was detected by flow cytometry. Western blot was used to assay the protein expression levels of phosphorylated （p）-Akt， Akt， p21. The glycolysis of 5637 cells was determined in glucose uptake and lactate secretion assays. ResultCompared with the blank group， erianin inhibited the proliferation of bladder cancer 5637 cells （P<0.05）. Overexpression of Akt partially reversed the inhibitory effect of erianin on the proliferation of bladder cancer 5637 cells （P<0.05）. Clone formation assay showed that erianin inhibited the clone formation of bladder cancer 5637 cells （P<0.05）， which was partially reversed by the overexpressed Akt （P<0.05）. As revealed by comparison with the blank group， erianin arrested the bladder cancer 5637 cells in G1 phase （P<0.05）， which was also reversed by the overexpressed Akt （P<0.05）. Western bolt showed that erianin promoted the expression of p21 but suppressed the expression of p-Akt and Akt （P<0.05）. By contrast， the overexpression of Akt down-regulated the elevated p21 protein expression induced by erianin （P<0.05）. Compared with the blank group， erianin inhibited the glucose uptake and lactate secretion of bladder cancer 5637 cells （P<0.05）. Overexpression of Akt weakened the inhibitory effect of erianin against the glycolysis of 5637 cells （P<0.05）. ConclusionErianin is able to inhibit the proliferation of bladder cancer 5637 cells， promote the expression of p21， and inhibit the expression of p-Akt. Overexpressed Akt reduces the inhibitory effect of erianin on the proliferation of bladder cancer 5637 cells， suggesting that Akt plays an important role in the inhibition of 5637 cell proliferation by erianin， which has provided a new target for the application of erianin in the treatment of bladder cancer.

Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021 / 生物医学与环境科学（英文）

Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

Mechanism of gubenfangxiaoyin drinking in the treatment of infantile asthma prevention by network pharmacology and molecular docking / 中国药理学通报

Aim To explore the mechanism of pediatric asthma based on network pharmacology and molecular docking technology. Methods Through TCMSP database, the chemical information and the targets of TCM chemical components and pediatric asthma targets in PubChem, SwissTargetPrediction and GeneCards were collected, and the intersection gene, namely the target gene of pediatric asthma was used. The “Drug-active ingredient-target” map was plotted with the Cytosacape 3.7.2 software. Protein interaction network maps were constructed based on the String database and analyzed by Cytoscape 3.7.2. GO and KEGG pathway analysis of acting targets using the Metascape database and bubbles were plotted on the Omicshare platform. Results A total of 238 active components and 11 corresponding 697 main targets were selected, 1 052 pediatric asthma disease target targets and 242 common targets were selected. Enrichment analysis found that common targets were primarily involved in biological processes such as MAPK cascade regulation and inflammatory response, as well as calcium signaling pathway, cAMP signaling pathway, AGE-RAGE signaling pathway, cGMP-PKG signaling pathway, etc. Molecular docking results showed that the active components of Astragalus(5'hydroxyiso-muronulatol-2',5'-di-O-Glucoside)docked well with the SRC, TP53, and IL-6 targets. We proved that anti-resistant drinking could down-regulate the expression of IL-6, SRC and TP53. Conclusions Gubenfangxiaoyin drinking may be involved in the regulation of the STAT3, SRC, AKT1, TP53, TNF, MAPK3, TP53,TNF,MAPK3 and IL6 and other targets, involved in the regulation of calcium-CAMP signaling pathway in childhood asthma, AGE-RAGE signaling pathway, cGMP-PKG signaling pathway, reduce the MAPK cascade, inflammatory response, etc, and play a role in the prevention and treatment of asthma.

Research progress of organophosphorus pesticides / organophosphorus nerve agents' protein adducts and formation mechanism / 中国药理学通报

Organophosphorus pesticides ( OPP) and organophosphorus nerve agents ( OPNAs) are both toxic organophosphorus compounds, which mainly exert toxic effects through irreversible inhibition of acetylcholinesterase ( AChE).This paper takes protein adducts as the research objective, studying the covalent adducts formed by OPP/OPNAs and different target proteins:endogenous scavengers ( butyrylcholinesterase, albumin, transfer-rin) and low-dose toxicity related proteins ( Cytoskeleton pro- tein, neuropathic target esterase, ubiquitin ) .The formation mechanism of protein adducts and the structural characteristics of active sites are reviewed for providing new ideas to confirm the exposure, trace, and accurate treatment and reasonable prevention of OP poisons in the future.

Cognition of Ovarian Cancer Microenvironment in Traditional Chinese Medicine from Perspective of "Yin-Yang Balance" / 中国实验方剂学杂志

Ovarian cancer， one of gynecological malignancies， is often diagnosed at the late stage because of the atypical early symptoms and has become a major killer of women. Research has found that the co-evolution of tumor cells and their surrounding microenvironment is an important cause for the occurrence and development of ovarian cancer. It is believed in traditional Chinese medicine （TCM） that Yin and Yang are the roots of everything， and their balance， namely Yin being at peace and Yang being compact （“Yin Ping Yang Mi”） is a sign of good health. The mutual opposition， restriction， and rooting of Yin and Yang as well as their waning and waxing and transformation are the keys to maintaining the balance. In TCM， ovarian cancer falls into the category of abdominal mass， which results from the struggle between healthy Qi and evil Qi. When the healthy Qi is deficient and the evil Qi is excessive， the balance between Yin and Yang will be destroyed， triggering the body and ovarian cancer microenvironment as well as the relevant factors in the inflammatory microenvironment to be mutually opposed， restricted， and transformed， highly consistent with the dynamic development of Yin and Yang. At present， the studies concerning TCM intervention in the inflammatory microenvironment of ovarian cancer mostly focus on the signaling pathways to reveal the advantages of TCM multiple components against cancer cells via multiple targets， but they fail to explain the TCM efficacy from the perspective of Yin-Yang balance. Therefore， guided by the concept of Yin-Yang balance， this paper macroscopically and microscopically explored the effects of the changed factors in inflammatory microenvironment on the occurrence and development of ovarian cancer， and put forward that the prevention and control principles of ovarian cancer should lie in the "adjustment of Yin-Yang balance"， accompanied by healthy Qi reinforcement and pathogen elimination. This paper has laid the foundation for the elucidation of modern research achievements regarding the ovarian cancer microenvironment with TCM theory and provide a theoretical basis for the clinical treatment of ovarian cancer with integrated TCM and western medicine.

Study Progress of Effect of Traditional Chinese Medicine Monomer in Intervening Ovarian Cancer by Regulating PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

Ovarian cancer is a kind of malignant tumor in female reproductive system with a high incidence. This disease is insidious at its early stage and the symptoms are not typical. Most of the patients have reached advanced stage by the time of diagnosis， seriously threating women's life and health. Many signaling pathways are involved in the formation and development of ovarian cancer， among which the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway is one of the key regulatory pathways. In recent years， traditional Chinese medicine （TCM） has obtained wide attention in treatment of tumors due to its advantages of high safety and less adverse reactions， and more and more attention has been paid to the study of TCM monomers. Molecular biology studies have shown that TCM monomers can play a role against tumor by regulating multiple targets. By reviewing the literature and searching several databases， we found that TCM monomer can play an important role in the growth， proliferation， invasion and migration， apoptosis， autophagy and reversal of drug resistance of ovarian cancer cells by regulating PI3K/Akt signaling pathway. According to the existing studies， TCM monomers have a certain effect on ovarian cancer， but there are still many problems. Although the mechanisms of some TCM monomers have been clarified in the treatment of ovarian cancer， such TCM monomers are only limited to the tumor-bearing nude mice in vivo and experimental studies on in vitro cells， and further studies are needed in the future. In addition， in the future researches， ovarian cancer syndrome differentiation and targeted therapy can be linked to the TCM flavors， efficacy and indications to further develop the advantages of TCM. Based on the current research situation at home and abroad， this paper summarized the research progress of targeted intervention of TCM monomers in ovarian cancer by regulating PI3K/Akt signaling pathway， in order to provide reference for further research of TCM monomers， and provide important ideas for the development of targeted treatment of ovarian cancer with TCM.

Progress in Research on Biomarkers of Post-Traumatic Epilepsy / 法医学杂志

Post traumatic epilepsy （PTE） is a serious complication of traumatic brain injury and a difficult problem in forensic justice practice. In recent years, many biomarkers have been applied to the diagnosis, treatment and prognosis of injuries and diseases. There have been many studies on the biomarkers of PTE in the field of epilepsy. This paper reviews the progress in research on biomarkers of PTE in recent years in order to provide reference for the forensic identification of PTE.

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (0.759, 0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (0.011, 0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (0.006, 0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% . 94.7%, (2)=4.123, 0.042) and PFS (5-year estimate, 66.7% . 94.7%, (2)=5.822, 0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group ((2)=4.881, 0.027); however, there was no statistical significance in 5-year PFS rate (0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% . 95.7%, (2)=6.285, 0.012; PFS: 65.5% . 91.3%, (2)=5.405, 0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

MiR-124-3p Enhances the Sansitivity of Chronic Myelogenous Leukemia Cell K562-R to Imatinib by Targeting ABCA2 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and mechanism of miR-124-3p-targeing regulating ABCA2 on chronic myelogenous leukemia cell K562-R.@*METHODS@#CML cells with miR-124-3p-overexpression and ABCA2-over-expression as well as subcutaneoustrans planted tumor nude mice were used as study objects. And the CML cells were divided into four groups: K562-R blank control, miR-124-3p mimic control, ABCA2-overexpression and mimic+PC ABCA2. The effects of miR-124-3p and ABCA2 on CML cells were analyzed. The levels of proliferation-, apoptosis- and autophagy- related protein were determined by Western blot. qRT-PCR was employed to detect the levels of miR-124-3p and ABCA2 in K562-R cells. The relationship between miR-124-3p and ABCA2 was validated by luciferase reporter system assays and bioinformatics. Hoechst/immunohistochemical staining and CCK-8 assay were performed to investigate the function involved.@*RESULTS@#miR-124-3p highly expressed in K562-S cells and lowly expressed in K562-R cells, however, ABCA2 lowly expressed in K562-S cells and highly expressed in K562-R cells. Over-expression of miR-124-3p significantly decreased ABCA2 level and cell growth, but increased autophagy and apoptosis in K562-R cells (P＜0.01). When ABCA2 was over-expressed, the K562-R cell growth was promoted and autophagy and apoptosis were inhibited (P＜0.01). The miR-124-3p promoted cell autophagy and apoptosis but inhibited cell growth in nude mice transplant tumor model (P＜0.01).@*CONCLUSION@#miR-124-3p can target ABCA2 to inhibit the growth of CML cells and promote the cell autophagy and apoptosis of CML cells.

Systematic analysis of protein expression in Candida albicans exposed to farnesol / 中华医学杂志(英文版)

Background@#The phenotypic switching of Candida spp. plays an important role in the development of vulvovaginal candidiasis (VVC). Farnesol, as a quorum-sensing molecule in Candida albicans, has the ability to prevent yeast-to-hyphal conversion in vitro. However, the mechanism underlying this ability is unclear. This study aimed to investigate changes in protein levels to better understand how farnesol impacts processes contributing to VVC.@*Methods@#The isobaric tag for relative and absolute quantitation technique was used to detect protein expression in C. albicans strain SC5314 (ATCC MYA-2876) with or without farnesol exposure. Proteins with a threshold fold change greater than 1.5 were screened and considered differentially expressed proteins. All the altered proteins were analyzed using Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and metabolic pathway annotation.@*Results@#Between the farnesol-exposed group and the farnesol-unexposd group, we detected 297 altered proteins among all 2047 tested proteins based on a threshold fold change of more than 1.5 (P < 0.05). Eighty-seven of the 297 altered proteins exhibited metabolic enzyme activity and participated in 85 metabolic pathways according to KEGG pathway analysis. Most of these metabolic pathways were associated with central carbon metabolism processes. In the sterol synthesis pathway, which involves the synthesis of farnesol, ERG25 (methylsterol monooxygenase) and ERG4 (delta 24(24(1))-sterol reductase) were both down-regulated in the farnesol-exposed group. All six altered proteases associated with the oxidative phosphorylation process were down-regulated in the farnesol-exposed group relative to the farnesol-unexposed group.@*Conclusions@#The mechanisms underlying farnesol-induced phenotype switching involves the adjustment of metabolic activities and epigenetic modification. Exogenous farnesol had an evident, but non-deterministic effect on the synthesis of ergosterol. The potential drug activity of farnesol warrants further investigation.

Optimization of Formulation of Erhuangsan Bletillae Rhizoma Gelatin Sustained Release Double-layer Membrane by Central Composite Design-response Surface Methodology / 中国实验方剂学杂志

Objective: With Bletillae Rhizoma gelatin as the main film-forming materials, Erhuangsan was developed into a sustained-release double-layer membrane for vagina. Method: Taking hydroxypropyl methyl cellulose(HPMC) and Bletillae Rhizoma gelatin as the film-forming materials of Coptidis Rhizoma-Alumen membrane layer, sodium carboxymethyl cellulose(CMC-Na) and Bletillae Rhizoma gelatin as the film-forming materials of Catechu membrane layer, glycerol as plasticizer, Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane was prepared.Central composite design-response surface methodology was used to optimize formulation of this preparation with appearance quality score, adhesion force and in vitro cumulative release as indexes. Result: Optimum formulation of Catechu membrane layer was 1.61% of CMC-Na, 3.81% of Bletillae Rhizoma gelatin and 8.49% of glycerol;optimum formulation of Coptidis Rhizoma-Alumen membrane layer was 1.15% of HPMC, 3.41% of Bletillae Rhizoma gelatin and 10.02% of glycerol. Conclusion: The optimized formulation is stable and feasible.Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane has characteristics of advanced dosage form and convenient use, providing a feasible modern Chinese medicine preparation for treatment of cervical cancer, and accumulating data for the research of Chinese medicine film agent.

Research Progress of Vaginal Mucosal Drug Delivery System / 中国实验方剂学杂志

Because it can not only directly reach the lesion site to play a local therapeutic effect, but also avoid the liver first pass effect and play a systemic therapeutic effect, vaginal mucosal administration has attracted more and more attention from domestic and foreign scholars in the treatment of vaginitis, cervicitis and other diseases. This article introduces the physiological characteristics of the vagina and discusses the factors affecting drug absorption. The vaginal mucosal drug-administered preparations, which are contained in the drug database of U.S. Food and Drug Administration(FDA) and China Food and Drug Administration(CFDA), and listed in the 2015 edition of Chinese Pharmacopoeia, are taken as the research objects. And the application of their dosage forms, indications and other aspects were sorted out and analyzed. The related literature on vaginal mucosal drug delivery systems in recent years was reviewed, and the dosages forms and in vitro and in vivo evaluation were summarized. Some problems in the study of vaginal mucosal drug preparations have been pointed out:①the western medicine preparations are widely used, and the related Chinese medicine preparations have been developed less; ②the majority of dosage forms are tablets, suppositories and other conventional dosage forms; ③there are few studies on the evaluation of vaginal mucosal preparations in vitro and in vivo. It is suggested that the future development of vaginal mucosal drug delivery system can be a useful attempt in the application of new technologies and methods, such as combination of drugs, high adhesion excipients, liposomes, etc;so as to provide reference for the application and improvement of vaginal mucosal drug delivery system.

Study on sesquiterpenes from agarwood originating from Gyrinops salicifolia / 中国中药杂志

Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4β,5β,7β-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC_(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC_(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].

Application Status and Research Progress of External Traditional Chinese Medicine Ointment for Rheumatism Treatment / 中国实验方剂学杂志

Due to the definite curative effect,stable drug properties and low incidence of adverse reactions,the external traditional Chinese medicine(TCM) ointment for rheumatism treatment has attracted more and more attention from scholars at home and abroad.Based on the external TCM ointment for the treatment of rheumatism approved by China Food and Drug Administration(CFDA),this paper would comb and analyze their dosage forms,varieties,specifications,etc.On the other hand,this article summarizes the application of the new formulation technology,prescription research,study on the forming process,pharmacodynamics and safety research,etc.The problems existing in this area were pointed out,such as lack of new preparations;less research on the penetration material basis,the penetration enhancing mechanism,and the penetration enhancing law;the selection of detection indicators of quality control standards is not comprehensive enough;qualitative and quantitative studies of pharmacokinetics are relatively scarce and so on.Meanwhile,proper measures and suggestions are put forward.Not only the formulation classification and specification description of external TCM ointment should be standardized,but also new dosage forms such as intelligentized,controlled release and targeted preparations of Chinese medicine should be actively introduced;the study of transdermal activity of transdermal enhancer itself should be strengthened,and investigating the correlation between the transdermal absorption of the agent itself and promoting transdermal absorption;the biological effect index or indicators that combine chemical and biological effects should be used,and learning from the latest research achievements of multidimensional spectroscopy of Chinese herbal medicine,thereby establishing scientific detection indicators and quality control methods that conform to modern transdermal concept.