Research on regulatory countermeasures for local human genetic resources in China / 中国医学伦理学

Human genetic resources are an indispensable part of national natural science and technology resources， as well as an important strategic resource for safeguarding national security， public health， and social public interests. To promote the effective protection and rational utilization of human genetic resources， as well as improve and optimize the local human genetic resources management system in China， this paper summarized the current situation of administrative approval and supervision of national human genetic resources from 2004 to 2021 by sorting out the national human genetic resources management policies and regulations. Furthermore， the current situation and progress of local human genetic resources management in China were understood from three aspects， including development planning and programs of human genetic resources， administrative licensing and penalties， and the construction of management expert committees. The main problems of local human genetic resources management in China were discussed and analyzed， such as unclear supervision， difficulty in supervision and inspection， and capacity for services. Based on the causes of the problems and the local management work， specific countermeasures and suggestions were put forward from the perspective of clarifying the regulatory policies and procedures for human genetic resources， improving the supervision and inspection mechanisms， and improving the management and service capabilities.

Detection and Validation of Chimeric RNA / 生物化学与生物物理进展

Chimeric RNA is a fusion transcript comprising of exon fragments from different genes. There are three splicing types: chromosome rearrangements, trans-splicing, cis-splicing, and the recently mentioned circular chimeric RNA. The traditional methods for the detection of chimeric RNA includes chromosome karyotype analysis, FISH, DNA microarray, etc., but their specificity, sensitivity and accuracy for the detection of chimeric RNA are poorly understood. With the development of sequencing technology, second-generation sequencing technology has shown strong data processing capabilities and can detect chimeric RNA through high-throughput sequence analysis. Currently, detection methods making use of high-throughput sequencing datasets includes FusionCatcher, SOAPfuse, EricScript, etc. For validation of the detected chimeric RNA, the commonly used methods include PCR, RPA, agarose gel electrophoresis, sanger sequencing, etc. The development of newly introduced techniques has led to the discovery of different novel chimeric RNA, the third and fourth generation sequencing has also been developed and nearly mature, and the sequencing technology taking PacBio as an example has also brought a new dawn to the discovery of chimeric RNA, but each of them has its advantages and disadvantages, mainly focusing on its cost, false positive rate, detection time, etc. This paper basically describes various different techniques that can be utilized for the detection and validation of chimeric RNA.

Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

Exploring the significance of chemotherapy in the perioperative application of biliary tract carcinomas / 中华外科杂志

Biliary tract cancer is extremely malignant with a poor prognosis. At the moment, the only curative method available is radical resection. Targeted and immunotherapy are currently advancing quickly, but chemotherapy still holds a key role in the perioperative management of biliary cancer. Perioperative chemotherapy aims to decrease tumor volume before surgery so that patients can have their tumors surgically removed or have a higher radical resection rate. It also aims to remove any tumor cells that remain after surgery and prevent the growth of new tumors. Chemotherapy-based combination treatment techniques have been increasingly investigated in recent years to improve perioperative care and patient survival. From the standpoint of chemotherapy regimens and clinical trial success in the perioperative phase of radical surgery, the value of chemotherapy in the perioperative period of biliary tract cancer were explored in this paper.

Survival analysis of patients with intrahepatic cholangiocarcinoma treated with adjuvant chemotherapy after radical resection based on CoxPH model and deep learning algorithm / 中华外科杂志

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Efficacy and safety of sindilizumab combined with intensity modulated radiotherapy and chemotherapy in patients with advanced cervical cancer / 中国药师

Objective To investigate the clinical efficacy and safety of sintilimab in combination with intensity-modulated radiotherapy(IMRT)and chemotherapy in patients with advanced cervical cancer(ACC).Methods The clinical data of ACC patients diagnosed and treated in the Department of Obstetrics and Gynecology of Xi'an Ninth Hospital from January 2019 to June 2020 were retrospectively collected.According to the treatment regimen,ACC patients were divided into Sintilimab group(sintilimab + IMRT combined with cisplatin and taxane)and control group(IMRT combined with cisplatin and paclitaxel).Serum tumor markers[squamous cell carcinoma antigen(SCCA),carcinoembryonic antigen(CEA),carbohydrate antigen 724(CA724)and carbohydrate antigen 199(CA199)],immune function[CD3+,CD4+ and CD8+]and quality of life[quality of life(QOL)scale assessment]were observed and compared before and after treatment.The short-term efficacy[objective response rate(ORR)and disease control rate(DCR)]and long-term efficacy[mortality,local recurrence rate,distant metastasis rate,and overall survival(OS)]in patients with ACC were compared.The occurrence of adverse drug reactions were assessed according to the American Radiation Oncology Collaboration(RTOG)and Common Terminology Criteria for Adverse Events.Results A total of 118 ACC patients were included in the study,including 59 patients in the sintilimab group and 59 in the control group.Before treatment,there were no significant differences in serum SCCA expression level,serum CEA expression level,serum CA724 expression level,serum CA199 expression level,CD3+,CD4+,CD8+/CD4+ and quality of life between the two groups(P>0.05).After treatment,the serum SCCA level,CEA expression level,CA724 expression level,serum CA199 expression level,CD3+,CD4+ and CD8+/CD4+ levels in the Sintilimab group were significantly lower than those in the control group(P<0.05),the quality of life and the ORR were significantly higher than that in the control group(P<0.05),while there was no significant difference in DCR between the two groups(P>0.05).The mortality rate,local recurrence rate and distant metastasis rate of ACC patients in the Sintilimab group were significantly lower than those in the control group(P<0.05).Kaplan-Meier analysis showed that the OS of ACC patients in the Sintilimab group was significantly higher than that in the control group(P<0.05).In addition,there was no statistically significant difference in adverse drug reactions between the Sintilimab group and the control group(P>0.05).Conclusion Sintilimab combined with IMRT and chemotherapy has significant efficacy in ACC patients,which can reduce the level of tumor markers,improve quality of life,reduce mortality,local recurrence rate and distant metastasis rate,and improve total OS,with high safety.

Congenital hypothyroidism in preterm infants:analysis of factors in the pathogenesis and clinical prognosis / 中国新生儿科杂志

Objective:To investigate the characteristics of congenital hypothyroidism (CH) in premature infants and analyze the predictors of transient congenital hypothyroidism(TCH) and permanent CH (PCH).Methods:A retrospective study was conducted on the preterm infants with CH born in Beijing from January 2008 to June 2018. They were screened, diagnosed and treated by the Beijing Neonatal Disease Screening Center. They were assigned into TCH and PCH groups according to the clinical prognosis. Univariate analysis and Logistic regression analyses were used to determine the predictors of PCH, and the receiver operating characteristic curve (ROC) was drawn to determine the best cut-off point.Results:A total of 2 216 892 newborns were screened, 15 382 were initially screened positive, the median time of screening was 4(4,10) d after birth, and the median time of postnatal reexamination was 30(22,42) d after birth, 14 576 newborns were reexamined, the reexamination rate was 94.8%. A total of 92 preterm infants were diagnosed with CH, of which 60 were TCH, accounting for 65.2%; 28 were PCH, accounting for 30.4%; and 4 were lost to follow-up, accounting for 4.3%. Univariate analysis showed that in the PCH group, the abnormal rate of thyroid B-ultrasound, levothyroxine (LT4) dose at 1-year old, thyrotropin (TSH) level at 2 years old, LT4 dose at 2 years old, LT4 dose and free thyroxine (FT4) level at 3 years old were higher than those in the TCH group. Logistic regression analysis revealed that abnormal B-ultrasound ( OR=12.184,95% CI 2.270~65.403), and elevated TSH level at 2 years old ( OR=2.033,95% CI 1.280~3.228),increased LT4 dose at 3 year old ( OR=21.435,95% CI 3.439~133.584) are the risk factors for PCH. The maximum area under ROC curve was 0.798 at 3 years old (95% CI 0.680~0.916), the best cut-off point was 1.3 μg/(kg·d) for the 3-year-old drug dose; followed by 2-year-old TSH level, which was 0.683 (95% CI 0.548~0.817), the best cut-off point was 4.51 μIU/ml. Conclusions:TCH accounted for a large proportion of preterm infants with CH. During the follow-up, the increased LT4 dose at 3 years old and the elevated TSH level at 2 years old were the early predictors of PCH.

Three-dimensional finite element study on the effects of maxillary anterior two-step retraction and en-masse retraction with clear aligners / 中华口腔医学杂志

Objective: To investigate the effects of two-step retraction and en-masse retraction on tooth movement pattern of anterior teeth and posterior anchorage with clear aligners using three-dimensional finite element analysis. Methods: A finite element model of maxillary first premolar extraction case undergoing clear aligner treatment was established based on maxillofacial cone-beam CT data of a 24-year-old adult male with individual normal occlusion, who visited Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine for impacted mandibular third molar in June, 2022. The initial tooth displacement of five anterior retraction protocols (two-step with canine retraction, two-step with incisor bodily retraction, two-step with incisor retraction-overtreatment, en-masse bodily retraction, and en-masse retraction-overtreatment) were evaluated. Results: Two step with canine retraction caused distal tipping of the canine and labial tipping of the incisors (0.18° for central incisor and 0.13° for lateral incisor). Two step with incisor retraction caused mesial tipping of the canine. In two step with bodily retraction protocol, uncontrolled lingual tipping was found in central incisor (0.29°) and lateral incisor (0.32°). In two-step with incisor retraction-overtreatment protocol, the movement pattern of the incisors didn't change, but the inclinations reduced to 0.21° and 0.18°. En-masse retraction caused distal tipping of the canine. In en-masse bodily retraction protocol, uncontrolled lingual tipping was also found in central incisor (0.19°) and lateral incisor (0.27°). In en-masse retraction-overtreatment protocol, the central incisor showed controlled lingual tipping (0.02°) and the lateral incisor showed palatal root movement (0.03° labial inclination). Posterior teeth exhibited mesial tipping in all five protocols. Conclusion: En-masse retraction with incisor overtreatment was beneficial to incisor torque control in clear aligner treatment.

Biological Implication of Chimeric RNAs in Cancer / 中国生物化学与分子生物学报

Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.

Molecular biological characteristics of the 2019 novel Coronavirus in Shijiazhuang / 中华检验医学杂志

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.

Development of the iGEM high school track / 生物工程学报

The international genetically engineered machine (iGEM) competition is a global top college academic competition in synthetic biology. The iGEM competition has exhibited extensive international influence and attracted teams from more than 40 countries and regions around the world to participate in. The annual iGEM outputs have attracted the attention of top academic journals or international media such as Science, Nature, Scientific American, The Economist, British Broadcasting Corporation (BBC), etc. High school teams participated in iGEM since 2011, and the number of high school teams has increased year by year. High school participants are increasingly becoming one of the most important forces to promote the development of iGEM and synthetic biology. IGEM competition has also become an important platform to foster the core literacy of high school students. This paper summarized the track rules, topic selection tendency and awards of high school teams based on data of 2017 to 2021 iGEM competition. In addition, we analyzed the significance of iGEM competition on fostering of high school students' core literacy and discussed the development trend of global high school teams, with the aim to provide a reference for high school team building in the future.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

The Formation Mechanism and Functional Implication of Chimeric RNAs / 中国生物化学与分子生物学报

Traditionally, chimeric RNA is thought to be generated by chromosome rearrangement, and its products (RNAs and proteins) were once considered as unique features of cancer. However, with the advancement of next-generation sequencing technologies and the development of bioinformatics software tools, increasing numbers of chimeric RNAs are being identified from various RNA-Seq database. Recently, numerous chimeric RNAs were discovered in human normal tissues and cell lines, with physiological functions. Besides chromosome rearrangement, chimeric RNAs are formed by different molecular mechanisms, including trans-splicing, cis-splicing of adjacent genes. Chimeric RNAs, without chromosomal changes, are regulated at the transcriptional level, and they show specific physiological functions and regulation patterns. Their dysregulation may induce cell differentiation and tumorogenisis. In addition, chimeric RNAs also play roles in normal cell growth and/or migration, cell cycle and apoptosis, induce genomic aberration by influencing chromosome rearrangement, act as potential competitive endogenous RNA, and influence stem cell differentiation. The expression of chimeric RNAs in specific tissues and cell development stages has the potential to be used as diagnostic and therapeutic biomarkers. Histological mapping studies can improve the specificity of treatment for unique cell types, and the chimeric RNA provides a new perspective to achieve this goal. The widespread existence of chimeric RNAs suggests that they may extend the diversity of genomes in human and higher animals.

Traditional Chinese medicine targeting cancer stem cells as an alternative treatment for hepatocellular carcinoma / 中西医结合学报

Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.

The diagnosis and treatment of ectopic ureter with bladder neck and urethral maldevelopment in children / 中华泌尿外科杂志

Objective:To discuss the diagnosis and treatment of ectopic ureter company with the bladder neck and urethral maldevelopment in children.Methods:The clinical data of the 6 patients admitted to Children’s Hospital affiliated to Chongqing Medical University from September 1993 to April 2019 diagnosed as ectopic ureter company with the bladder neck and urethral maldevelopment were retrospectively reviewed. The 6 children were girls and the median age was 7 years old , ranged from 2 to 15 years old. All children had ectopic ureter, including 3 in left-sided, 1 in right-sided, and 2 in bilateral-sided. Five children presented the intermittent dribbling incontinence and one child presented the continuously incontinence without normal voiding. Through ultrasound, IVP, MRI, cystoscopy and retrograde urography, seven ureters were found ectopic position, including bladder neck in 4 cases, two ureters inserted in the vagina in 2 cases. There were two cases with duplex kidney and 4 cases with renal dysplasia. Preoperative cystoscopy revealed wide and short urethra in 1 case, wide bladder neck combined with wide and short urethra in 4 cases. The surgery type included nephrectomy in cases 1-3, bilateral ureter reimplantation in case 4 who had the bilateral ectopic ureter , bilateral ureter reimplantation and bladder neck reconstruction at the same time in case 5. Nephrectomy associated with bladder neck and urethral reconstruction in case 6.Results:Five patients were followed-up and one patient was lost to follow-up after the first operation. Mean follow-up was 41.2 months (ranging 2 to 84 months). Four patients with bladder neck and maldevelopment that were not solved intraoperatively got reoperations due to incontinence without remission. Case 1, who underwent urethral reconstruction and extension, and urinary incontinence was partially relieved. Case 2 was found to have wide bladder neck deformity, and then retrospectively got bladder neck reconstruction and urethrovaginal fistula repair in 3 years and 5 years later. The urinary incontinence was completely relieved. The ureteral stump of case 3 was resected 2 years after operation due to recurrent urinary tract infection, and then got twice bladder neck and urethral reconstruction in 3 years and 6 years later of nephrectomy. His incontinence was partially relieved. The case 4 got bladder neck and urethral reconstruction in one year after bilateral ureter reimplantation, and incontinence was partially relieved too. Among the two patients underwent combined surgery, the case 5, who got bilateral ureteral bladder replantation combined with bladder neck reconstruction, were lost to follow-up after surgery. The case 6 got dysplasia nephrectomy combined with bladder neck reconstruction and urethroplasty were completely relieved of urinary incontinence.Conclusions:Bladder neck and urethra maldevelopment is one of the main causes of urinary incontinence after surgery in children with ectopic ureter. The diagnosis mainly relies on cystoscopy. The treatment mainly relies on surgery. Bladder neck and urethral reconstruction is expected to be available. If the operative conditions permit, synchronous surgical treatment of ectopic ureter and bladder neck and urethral maldevelopment will get a better prognosis than staging surgery.

Secondary Metabolites of Endophytic Fungus Trichoderma harzianum Isolated from Physalis angulata / 中国实验方剂学杂志

Objective:To study the secondary metabolites of the endophytic fungus Trichoderma harzianum,which was isolated from Physalis angulata. Method:The strains were cultured in a big-scale by oscillating incubator. Then the obtained culture liquid and mycelia were extracted by EtOAC and actone,respectively. The extracts were integrated after recovery of solvents, and then the active secondary metabolites were isolated and purified by comprehensive use of open ODS flash column,sephadex LH-20,HPLC,and LC-MS analysis techniques. Their structures were identified according to their physico-chemical properties and nuclear magnetic resonance (NMR) data. The cytotoxicities of the compounds were determined by methyl thiazolyl tetrazolium(MTT) assay. Result:Ten compounds isolated from T. harzianum were identified as destruxin A2(1),destruxin B2(2),3-isobutyl-pyrrolopiperazine-2,5-dione[cyclo (leu-pro dipeptide)](3),cyclo (Phen-pro) dipeptide(4),cyclonerodiol(5),brevianamide F(6),N-acetyltryptamine(7),9-hydroxyl-(2-methylpropyl) isobutyl phthalate(8),5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone(9),and phenylpropionic acid(10). Compounds 1-10 didn't exhibit significant cytotoxicity to lung cancer cell line A549 in the MTT assay (IC50 ≥ 20 mg·L-1). Conclusion:All compounds were isolated from T. harzianum for the first time.

An exploration of the application of a new training mode of special coronary artery bypass grafting in postgraduate education / 中华医学教育探索杂志

Objective To compare the effects between the dual-cycle intensive training mode (DCITM) of "teaching-in vitro-in vivo-summary-in vitro-in vivo-assessment" and the single-cycle basic training mode (BTM) of "teaching-in vitro-tn vivo-assessment" on training graduate students majoring in cardiovascular surgery.Methods Eight graduate students majoring in cardiovascular surgery received the basic training of coronary artery bypass vascular anastomosis under the mode of BTM or DCITM.Then the training effects were evaluated by scoring of experts.Besides,SPSS 17.0 statistical software was used to analyze the evaluation results.Results Compared with students who received BTM,the postgraduates trained by DCITM became more skilled in vascular anastomosis.In vitro,the average number of anastomosis completed by trainee increased significantly [(2.0 ± 1.0) vs.(5.0 ± 1.5),P＜0.05] over a specified period of time,the vascular leakage rate was significantly reduced [(92 ± 5)％ vs.(30 ± 2)％,P＜0.05],and the average time per anastomosis was significantly shorter [in vitro:(20.1 ± 2.5) min vs.(12.6 ± 3.3) min,P＜0.05].There was also a statistically significant difference in the average time of each anastomosis in miniature pigs with coronary vascular anastomosis [in vivo:(30 ± 2) min vs.(21 ± 3) min,P＜0.05].Conclusion Taken into together,DCITM is a highly efficient mode for promoting the quality of cardiovascular-surgery-teaching and enhancing the effectiveness of training in clinical surgical skills.

Secondary metabolites of Streptomyces sp. A1693 / 中国中药杂志

By means of various chromatographic methods such as Sephadex LH-20，ODS，and semi-preparative HPLC，ten compounds were isolated from Streptomyces sp. A1693 and their structures were elucidated on the basis of spectroscopic data and physico-chemical methods. The compounds comprised 5 butenolides，2 diketopiperazines，and 3 antimycin antibiotics. The structures were identified as (5)-5-(11-hydroxymethyloctyl)furan-2(5)-one (1), (5)-5-(11-hydroxy-11-methylheptyl)furan-2(5)-one (2), (5)-5-(11-methyl-12-oxooctyl) furan-2(5)-one (3), (5)-5-(11-hydroxy-11-methyloctyl)furan-2(5)-one (4), (5)-5-(11-hydroxy-12-methyloctyl)furan-2(5)-one（5），cyclo-Phe-Val (6)，cyclo-Phe-Ile (7)，uranchimycin A (8)，uranchimycin B (9)，and deisovalerylblastomycin (10). Among them，1 was defined as a new compound. All the compounds didn't show the cytotoxic activity against A549 cell line (IC₅₀>50 mg·L⁻¹).