Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Advances in research on small molecule regulators targeting HBV cccDNA generation and transcription / 药学学报

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

Development of fibroblast activation protein-targeted molecular probes in non-neoplastic diseases / 中华核医学与分子影像杂志

Fibroblast activation protein (FAP) is an important molecular marker of cancer-associated fibroblasts (CAFs). FAP is selectively expressed in more than 90% of epithelial carcinomas, but barely expressed in normal tissues. In recent years, a variety of radiolabeled molecular probes based on FAP inhibitor (FAPI) have been developed and used for imaging of malignant tumors. FAP is also highly expressed in some non-neoplastic diseases related to chronic inflammation and tissue remodeling, including arthritis, atherosclerosis, fibrosis of myocardial infarction, cirrhosis, and idiopathic pulmonary fibrosis. FAPI imaging shows a potential in these diseases. This paper reviews the current status of radionuclide labeled FAPI and the application of which in non-neoplastic diseases.

Predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor / 中华核医学与分子影像杂志

Objective:To investigate the predictive values of 18F-FDG PET/CT image feature and metabolic parameters for the malignant potential of gastrointestinal stromal tumor (GIST). Methods:From March 2014 to June 2020, the 18F-FDG PET/CT imaging and surgical pathological data of 35 patients with GIST (27 males, 8 females; age 44-84 years) from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and Zhongnan Hospital of Wuhan University were analyzed retrospectively. Patients were divided into ring-shaped uptake group and other uptake patterns group according to 18F-FDG PET/CT image feature. Fisher′s exact test was used to analyze the differences of tumor necrosis and National Institutes of Health (NIH) risk classification (short for NIH classification) between different image feature groups. Mann-Whitney U test was used to analyze the differences of SUV max , metabolic parameters at different thresholds (2.5, 40%, 50%) of SUV max (metabolic tumor volume (MTV; MTV 2.5, MTV 40%, MTV 50%) and total lesion glycolysis (TLG; TLG 2.5, TLG 40%, TLG 50%)) between different clinicopathological features (lesion location, tumor diameter, mitotic count, Ki-67, necrosis, image feature, NIH classification) groups. Spearman rank correlation analysis was used to explore the correlation between clinicopathological features and metabolic parameters. ROC curve analysis was used to distinguish NIH classification of different metabolic parameters. Delong test was used to compared differences between different AUCs. Results:Of 35 GIST patients, 11(31.4%) were ring-shaped uptake and 24(68.6%) were other uptake patterns, and the differences of necrosis (7/11 vs 12.5%(3/24); P=0.004) and NIH classification (11/11 vs 25.0%(6/24); P<0.001) between the two groups were significant. There were significant differences of metabolic parameters between different groups of tumor diameter, mitotic count, necrosis, image feature, NIH classification ( z values: from -4.70 to -2.09, all P<0.05), while there were no significant differences of Ki-67 ( z values: from -0.83 to -0.71, all P>0.05). Metabolic parameters were correlated with mitotic count, tumor diameter, necrosis, image feature and NIH classification ( rs values: 0.36-0.81, all P<0.05), while was not correlated with Ki-67 ( rs values: 0.12-0.14, all P>0.05). The differences of AUCs between SUV max and MTV 2.5, TLG 2.5, TLG 40%, TLG 50%were significant (0.752, 0.856, 0.856, 0.882, 0.886; z values: 1.96-2.12, all P<0.05). Conclusions:The NIH classification of GIST with ring-shaped uptake on 18F-FDG PET/CT is higher and more prone to necrosis. The 18F-FDG PET/CT metabolic parameters based on different thresholds of SUV max have certain significance for the prediction of NIH classification of GIST, and may be superior to SUV max.

Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia / 中华医学杂志(英文版)

BACKGROUND@#Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.@*METHODS@#We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.@*RESULTS@#The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).@*CONCLUSIONS@#The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR 1800018895.

Effect of video games training on the gross motor skills of children with cerebral palsy: systematic review and meta-analysis / Efecto del entrenamiento con videojuegos en la motricidad gruesa de niños con parálisis cerebral: revisión sistemática y meta-análisis

Abstract The purpose of this work was to systematically evaluate the intervention effects of video games training (VGT) on the gross motor skills (GMS) development of children with cerebral palsy (CP). Seven Chinese and English databases (PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, EBSCO) were searched. Data were retrieved from randomized controlled trials on the GMS among individuals with CP. The retrieval was from the inception of each database to March 16, 2021. The included studies were evaluated quantitatively using the PEDro Scale. Then, relevant data were inputted and analyzed in Review Manager 5.4. Thirteen papers were included: seven written in English and six in Chinese. In the three subordinate concept of GMS, VGT could significantly improve locomotor skills (LS) (standardized mean difference = 0.80, 95% confidence interval 0.55-105, P<0.00001), and non-locomotor skills (NLS) (standardized mean difference = 0.83, 95% confidence interval 0.38-1.28, P=0.0003) in CP. However, there was no significant difference in object control skills (OCS), when compared with the control group (standardized mean difference = 0.55, 95% confidence interval -0.01-0.72, P=0.05). VGT can improve LS and NLS in CP, but the effect on OCS is uncertain; therefore, it is recommended that additional high-quality literature be included in the future. In general, VGT has been proven an effective intervention tool on the GMS development in CP.

Resumen Este artículo intentó evaluar sistemáticamente el efecto de la intervención del entrenamiento con videojuegos (VGT) en el desarrollo de las habilidades motoras gruesas (GMS) de niños con parálisis cerebral (CP), basándose en un cuerpo de datos logrado de las conclusiones de pruebas controladas aleatorias sobre las habilidades motoras gruesas de niños con CP, obtenidos de la búsqueda sistemática en siete bases de datos chinos y extranjeros, tales como PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang y EBSCO. El lapso de búsqueda fue desde la fecha de establecimiento de cada base de datos hasta el 16 de marzo del 2021. Se aplicó la escala PEDro para realizar un estudio cuantitativo y después, se analizaron los datos relevantes con Review Manager 5.4. Se incluyeron 13 publicaciones, 7 artículos escritos en inglés y 6 en chino. En el marco del concepto de los tres subordinados de GMS, la VGT podría mejorar significativamente la habilidad locomotora (LS) (diferencia de medias estandarizada = 0.80, intervalo de confianza del 95%: 0.55-105, P<0.00001), y las habilidades no locomotoras (NLS) (diferencia de medias estandarizada = 0.83, intervalo de confianza del 95%: 0.38-1.28, P= 0,0003) en PC; pero no hubo una diferencia significativa en las habilidades de control de objetos (OCS), cuando se compararon con el grupo control (diferencia de medias estandarizada= 0,55, intervalo de confianza del 95% -0,01-0,72, P= 0,05). En conclusión, el VGT puede mejorar las LS y NLS en CP, pero el efecto sobre OCS es incierto; por lo que se recomienda la inclusión de literatura adicional de alta calidad en el futuro. De este modo se pudo demostrar que el VGT es una herramienta de intervención eficaz en el desarrollo de las GMS en niños con CP.

The SACT Template: A Human Brain Diffusion Tensor Template for School-age Children / 神经科学通报·英文版

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

Frequency-Resolved Connectome Hubs and Their Test-Retest Reliability in the Resting Human Brain / 神经科学通报·英文版

Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks. However, most resting-state functional magnetic resonance imaging (R-fMRI) studies have identified functional hubs by examining spontaneous fluctuations of the blood oxygen level-dependent signal within a typical low-frequency band (e.g., 0.01-0.08 Hz or 0.01-0.1 Hz). Little is known about how the spatial distributions of functional hubs depend on frequency bands of interest. Here, we used repeatedly measured R-fMRI data from 53 healthy young adults and a degree centrality analysis to identify voxelwise frequency-resolved functional hubs and further examined their test-retest reliability across two sessions. We showed that a wide-range frequency band (0.01-0.24 Hz) accessible with a typical sampling rate (fsample = 0.5 Hz) could be classified into three frequency bands with distinct patterns, namely, low-frequency (LF, 0.01-0.06 Hz), middle-frequency (MF, 0.06-0.16 Hz), and high-frequency (HF, 0.16-0.24 Hz) bands. The functional hubs were mainly located in the medial and lateral frontal and parietal cortices in the LF band, and in the medial prefrontal cortex, superior temporal gyrus, parahippocampal gyrus, amygdala, and several cerebellar regions in the MF and HF bands. These hub regions exhibited fair to good test-retest reliability, regardless of the frequency band. The presence of the three frequency bands was well replicated using an independent R-fMRI dataset from 45 healthy young adults. Our findings demonstrate reliable frequency-resolved functional connectivity hubs in three categories, thus providing insights into the frequency-specific connectome organization in healthy and disordered brains.

Tracing investigation and analysis of a Clostridium botulinum food poisoning incident in Bayingolin Mongolian Autonomous Prefecture, Xinjiang / 中华预防医学杂志

To analyze a suspected case of Clostridium botulinum food poisoning in Bayingolin Mongolian Autonomous Prefecture, Xinjiang and to help validating the diagnosis and providing technical support for clinical treatment. The basic information and clinical manifestations of food poisoning cases were investigated by using the epidemiological method of food safety accidents. The botulinum toxin genes in the samples were detected by real-time PCR and inoculation of KM mouse. The enriched bacteria were further purified and validated. PFGE and cluster analysis were performed on five isolates. Clostridium botulinum type A was detected in two homemade fermented bean samples and stool lavage fluid samples of three patients from enriched samples by toxin test and real-time PCR, and were further validated after isolation of Clostridium botulinum. PFGE showed 100% homology among five isolates. Five isolates of bacteria isolated from the stool lavage fluid of three patients and two homemade fermented bean curd were identified as the same source through PFGE. The cause of this food poisoning cases is food pollution of Clostridium botulinum type A.

Establishment and identification of human immortalized keratinocytes stably expressing human papillomavirus type 16 E6/E7 gene / 中华皮肤科杂志

Objective:To construct human immortalized keratinocytes stably expressing human papillomavirus type 16 (HPV16) E6/E7 gene, and provide a cell model for studying mechanisms underlying HPV16 E6/E7-induced cell immortalization and malignant transformation.Methods:Primary human foreskin keratinocytes (HFKs) were isolated by sequential two-step enzymatic digestion. Cultured HFKs were stably transfected with a HPV16 E6/E7 gene-overexpressing lentiviral vector LV5-HPV16 E6/E7, and consecutively cultured for more than 30 passages. Then, immortalized keratinocytes were screened out and divided into 3 groups: (1) blank control group: second-passage primary HFKs; (2) experimental group: HFKs transfected with LV5-HPV16 E6/E7 at different passages, and the second-passage primary HFKs transfected with LV5-HPV16 E6/E7 were referred to as A0 cells, thereafter, the transfected HFKs were named according to their passage number, such as A1, A2, ... A30; (3) positive control group: the HPV16-positive cervical cancer cell line SiHa. Real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the mRNA expression of HPV16 E6/E7 and protein expression of HPV16 E6/E7 and CK14, respectively, in the blank control group, experimental group and positive control group. Cell counting kit-8 (CCK8) assay and Transwell insert invasion assay were conducted to assess the cellular proliferative and invasive activity. In vivo tumor formation experiment in nude mice was conducted to investigate the tumorigenicity of A30 cells in the experimental group and SiHa cells in the positive control group. Results:Primary HFKs were successfully isolated. After the primary HFKs were transfected with the recombinant plasmid LV5-HPV16 E6/E7, the blank control group showed no fluorescence in the cells, but showed senescent phenotypes after serial passages, while in the experimental group, the volume and morphology of A30 cells were similar to those of the primary HFKs with the proportion of fluorescence-positive cells being 100%. Compared with the blank control group, the experimental group showed significantly increased mRNA expression levels of HPV16 E6 and E7 in A1, A10, A20 and A30 cells (HPV16 E6: t = 7.12, 8.07, 6.53, 5.66, P < 0.001, < 0.001, = 0.001, = 0.005, respectively; HPV16 E7: t = 3.20, 4.29, 3.75, 4.22; P = 0.024, 0.008, 0.013, 0.014, respectively) . The protein expression of HPV16 E6/E7 was absent in the blank control group, but was observed in A30 and SiHa cells. CCK8 assay showed that the proliferative activity of A10, A20 and A30 cells was significantly higher than that of the blank control group ( t = 6.49, 7.55, 9.43, P = 0.003, 0.002, 0.001, respectively) , while there was no significant difference in the proliferative activity between A1 cells and the blank control group ( t = 2.40, P = 0.074) . Transwell insert invasion assay showed that A30 cells could not cross the basement membrane, but SiHa cells could pass through the basement membrane and were stained blue. Two months after the inoculation with A30 cells in the nude mice, no visible tumors were found, which was confirmed by a histological study. Subcutaneous tumors were formed in the nude mice after the inoculation with SiHa cells. Conclusion:Human immortalized keratinocytes were successfully established by lentivirus-mediated transfection with HPV16 E6/E7 gene, and can serve as an ideal cell model for HPV-related research.

Desloratadine combined with Tongqiao Biyan capsule for the treatment of allergic rhinitis / 中国基层医药

Objective:To investigate the effects of desloratadine combined with Tongqiao Biyan capsule on allergic rhinitis. Methods:100 patients with allergic rhinitis who received treatment in The Affiliated Hospital of Medical College of Ningbo University from February 2018 to February 2020 were included in this study. They were randomly assigned to receive treatment with either desloratadine tablets (control group, n = 50) or desloratadine tablets combined with Tongqiao Biyan capsule (observation group, n = 50) for 21 days. Improvement in clinical symptoms and changes in inflammatory factors were observed in each group. Results:Scores of nasal itch, nasal obstruction, runny nose, and sneezing in the observation group were (1.42 ± 0.10) points, (1.20 ± 0.13) points, (1.25 ± 0.13) points, and (1.33 ± 0.14) points, respectively, which were significantly lower than those in the control group [(1.80 ± 0.12) points, (1.68 ± 0.15) points, (1.68 ± 0.11) points, (1.68 ± 0.13) points, t = 17.20, 17.10, 17.85, 12.95, all P < 0.001]. After treatment, interleukin -4, -6, -8 levels in the observation group were (16.12 ± 5.05) ng/L, (5.33 ± 2.10) ng/L, (37.16 ± 9.80) ng/L, respectively, which were significantly lower than those in the control group [(21.52 ± 5.58) ng/L, (8.12 ± 2.15) ng/L, (48.55 ± 9.65) ng/L, t = 5.07, 6.56, 5.86, all P < 0.05]. Interferon-γ level was significantly higher in the observation group than in the control group [(26.58 ± 2.58) ng/L vs. (23.68 ± 2.69) ng/L, t = 5.50, P < 0.001]. After treatment, the total score of the quality of life questionnaire was significantly higher in the observation group than in the control group [(61.58 ± 8.57) points vs. (40.98 ± 8.35) points, t = 12.17, P < 0.001]. There was no significant difference in total incidence of adverse reactions between observation and control groups [10.00% (5/50) vs. 14.00% (7/50), χ2 = 0.38, P > 0.05]. Conclusion:Desloratadine combined with Tongqiao Biyan capsule can better improve the symptoms of allergic rhinitis and better reduce inflammation without increasing adverse drug reactions compared with desloratadine alone.

Elevation of C-reactive protein early after cardiopulmonary bypass surgery is associated with occurrence of postoperative atrial fibrillation / 南方医科大学学报

OBJECTIVE@#To explore the association between postoperative C-reactive protein (CRP) levels and the occurrence of postoperative atrial fibrillation in patients undergoing cardiopulmonary bypass surgery.@*METHODS@#We retrospectively analyzed the data of 550 patients undergoing cardiopulmonary bypass surgery in our hospital from September, 2018 to May, 2021, and after screening against the exclusion criteria, 363 patients were selected for further analysis. Univariate analysis was used to analyze the correlation of age and early postoperative CRP level with the occurrence of postoperative atrial fibrillation, and Chi-square test was used to explore the correlation of gender, disease type, and comorbidity with postoperative atrial fibrillation followed by multivariate analysis of the data using a binary logistic regression model.@*RESULTS@#The 363 patients enrolled in this study included 247 with valvular disease, 42 with aortic dissection, 37 with coronary heart disease, and 37 with congenital heart disease, with a median postoperative CRP level of 88.65 mg/L and a median age of 57 years (range 5-77 years). Postoperative atrial fibrillation occurred in 101 (27.82%) of the patients, who were subsequently divided into atrial fibrillation group and sinus group. Univariate and multivariate correlation analyses showed that early postoperative elevation of CRP level was an important factor contributing to the occurrence of postoperative atrial fibrillation.@*CONCLUSION@#Early postoperative elevation of CRP level is associated with the occurrence of atrial fibrillation following cardiopulmonary bypass surgery.

Comparative study the curative effect, ventricular remodeling and cardiac function of patients in different left atria size undergoing valve replacement with " X" ablation of posterior left atrium wall / 中华胸心血管外科杂志

Objective:To investigate the influence of left atrial size on the ablation efficacy, cardiac morphology and function after valve replacement combined with X-type radiofrequency ablation on posterior wall of left atrium.Methods:From January 2015 to December 2019, 416 patients with mitral valve disease complicated with atrial fibrillation were divided into two groups according to the size of left atrium(Anteroposterior diameter 60 mm). Valve replacement combined with " X" radiofrequency ablation on posterior wall of left atrium was performed. The clinical data were analyzed retrospectively.Results:Except for the AF types, gender, length of stay and postoperative complications, other clinical data, operative and perioperative indicators were better in small left atria group(SLA)than in large left atria group(LLA). The differences were statistically significant( P<0.05). Fractional shortening(FS), ejection fraction(EF) in SLA at any time point were higher than that in LLA, P<0.05. The sinus rhythm conversion rates, the change rate of LA anteroposterior diameter in SLA at postoperative time points were higher than that in LLA, P<0.05. There was no significant difference of cardiac troponin(cTn) and myoglobin(MYO) between the two groups in 6 months after operation, P>0.05. The B-type natriuretic peptide(BNP), cTn, MYO in the other time points were lower than that in LLA, P<0.05. Conclusion:Larger left atrium reduces the rate of sinus rhythm conversion and maintenance in patients undergoing valve replacement combined with fibrillation ablation. There were worse ventricular remodeling and cardiac function recovery. Preoperative evaluation of left atrial size is helpful for prognosis.

Research Progress in Hepatocyte Growth Factor/Mesenchymal-epithelial Transition Factor Signaling Pathway:Effects and Mechanisms on Resistance to Targeted Therapy for Non-small Cell Lung Cancer / 中国医学科学院学报

Targeted therapy is an important therapeutic method for advanced non-small cell lung cancer with driver gene alteration.However,resistance to targeted therapy will inevitably happen in clinical practice,which has become a major issue demanding prompt solution.Studies have demonstrated that bypass resistance mediated by the activation of hepatocyte growth factor(HGF)/mesenchymal-epithelial transition factor(MET)signaling pathway is a common cause of resistance to targeted therapy.Presently,relevant studies have accumulated rich experience in the specific mechanisms.To be brief,HGF/MET is an important target for overcoming the resistance to targeted therapy and promises to be a leading biomarker for judging and observing the occurrence of resistance.This paper introduces the recent studies concerning the effects and mechanisms of HGF/MET signaling pathway on resistance to targeted therapy.

Research on inheritance of Professor WANG Jie's Experience in Treatment of Frequent Ventricular Premature Complexes Based on Inheritance Support System of Traditional Chinese Medicine / 中国实验方剂学杂志

Objective:With the aid of the Inheritance Support System of Traditional Chinese Medicine V2.5 （TCMISS V2.5），to study the experience and prescription rules of professor WANG Jie in the treatment of frequent ventricular premature complexes，and inherit his clinical experience in diagnosis and treatment. Method:Professor WANG Jie's medical records and prescriptions for frequent ventricular premature complexes from 2016 to 2020 were collected and sorted out. Improved mutual information method，association rules，complex system entropy clustering，and unsupervised entropy hierarchical clustering were used to analyze the nature and flavor，channel tropism，concerted application rules，pair and combination of herbs for statistics， association rules analysis and discovery of new prescriptions. Result:A total of 122 prescriptions of professor WANG Jie on the treatment of frequent ventricular premature complexes were collected. 110 herbs，mostly with pungent and sweet flavors，were mainly on spleen channel and also on heart，kidney，liver，lung，and stomach channels. Cinnamomi Ramulus，Paeoniae Alba Radix<italic>，</italic>Os Draconis<italic>，</italic>Ostreae Concha<italic>， </italic>Glycyrrhizae Radix<italic>，</italic>and Jujubae Fructus<italic> </italic>had the highest frequency in use. The high-frequency herbal pair was Cinnamomi Ramulus-Paeoniae Alba Radix（116 times， accounting for 95.08%），the commonly used corner drugs were Cinnamomi Ramulus<italic>-</italic>Os Draconis<italic>-</italic>Ostreae Concha<italic> </italic>（108 times，88.52%），Cinnamomi Ramulus<italic>-</italic>Paeoniae Alba Radix<italic>-</italic>Ostreae Concha （106 times， 86.89%），Cinnamomi Ramulus<italic>-</italic>Paeoniae Alba Radix<italic>-</italic>Os Draconis （106 times，86.89%）. Commonly used herbal pair was<italic> </italic>Aucklandiae Radix-Amomi Villosi Fructus. The core prescription herbs included Cinnamomi Ramulus<italic>-</italic>Paeoniae Alba Radix<italic>-</italic>Os Draconis<italic>-</italic>Ostreae Concha<italic>-</italic>Glycyrrhizae Radix<italic>-</italic>Jujubae Fructus<italic>-</italic>Zingiberis Recens Rhizoma<italic>-</italic>Achyranthis Bidentatae Radix<italic>-</italic>Codonopsis Radix<italic>-</italic>Astragali Seu Hedysari Radix<italic>-</italic>Cistanches Herba-Poria<italic>-</italic>Ziziphi Spinosae Semen. Conclusion:Professor WANG Jie's prescription for the treatment of frequent ventricular premature complexes is Guizhi Jia Longgu Mulitang，and the main herbs are Cinnamomi Ramulus，Paeoniae Alba Radix，Os Draconis，Ostreae Concha，Glycyrrhizae Radix，and Jujubae Fructus. The final prescription could be adjusted according to the diseases and symptoms of patients.

Exploration of active components and mechanism of Scutellariae Radix-Phellodendri Chinensis Cortex drug pair in treatment of psoriasis based on network pharmacology and molecular docking / 中国中药杂志

This paper aims to explore active components and mechanism of Scutellariae Radix(SR)-Phellodendri Chinensis Cortex(PCC) drug pair in treatment of psoriasis by network pharmacology and molecular docking. Specifically, the chemical components of SR and PCC were retrieved from literature and TCMSP, as well as targets of these components from PharmMapper and UniProt, and the targets related to psoriasis from OMIM, TTD, PharmGkb, and DrugBank. Then the chemical component-medicinal target, protein-protein interaction(PPI), and chemical component-psoriasis target networks were constructed by Cytoscape. Gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed based on Metascape. Finally, molecular docking of the chemical components(high degree) with core therapeutic targets was carried out by AutoDock vina. The results showed 88 compounds of SR and PCC(including baicalin, wogonoside, berberine and phellodendrine) and 30 targets of the pair in the treatment of psoriasis. The 30 targets mainly involved the biological processes such as neutrophil mediated immunity(GO: 0002446) and T cell activation(GO: 0042110), and the signaling pathways such as metabolism of xenobiotics by cytochrome P450(hsa00980), apoptosis(hsa04210), and PI3 K-Akt signaling pathway(hsa04151). The results of molecular docking demonstrated that the main active components can spontaneously bind to the targets and the binding energy of 46 components with epidermal growth factor receptor(EGFR) was less than-8 kcal·mol~(-1). According to the PPI analysis, EGFR may be a key target for the treatment of psoriasis. Active components such as baicalin and berberine had high binding affinity with EGFR. This study preliminarily revealed the multi-component, multi-target and multi-pathway mechanism of SR-PCC drug pair in the treatment of psoriasis, which provided theoretical basis for the research on the mechanism of the drug pair in the treatment of psoriasis.

Mapping Domain- and Age-Specific Functional Brain Activity for Children’s Cognitive and Affective Development / 神经科学通报·英文版

The human brain undergoes rapid development during childhood, with significant improvement in a wide spectrum of cognitive and affective functions. Mapping domain- and age-specific brain activity patterns has important implications for characterizing the development of children’s cognitive and affective functions. The current mainstay of brain templates is primarily derived from structural magnetic resonance imaging (MRI), and thus is not ideal for mapping children’s cognitive and affective brain development. By integrating task-dependent functional MRI data from a large sample of 250 children (aged 7 to 12) across multiple domains and the latest easy-to-use and transparent preprocessing workflow, we here created a set of age-specific brain functional activity maps across four domains: attention, executive function, emotion, and risky decision-making. Moreover, we developed a toolbox named Developmental Brain Functional Activity maps across multiple domains that enables researchers to visualize and download domain- and age-specific brain activity maps for various needs. This toolbox and maps have been released on the Neuroimaging Informatics Tools and Resources Clearinghouse website (http://www.nitrc.org/projects/dbfa). Our study provides domain- and age-specific brain activity maps for future developmental neuroimaging studies in both healthy and clinical populations.

Opinions on the corona virus disease 2019 / 重庆医学

The corona virus disease 2019 (COVID-19) has drawn much attention lately. It has the characteristics of hidden infection sources, diverse transmission channels, great differences in clinical characteristics and limited diagnostic methods. Additionally, the population is generally susceptible, and no specific medicines are available now, therefore, the prevention and control of the disease faces greater challenges. Mastering the characteristics of it for comprehensive prevention and control is the main strategy against the disease. This article systematically expounded the latest understanding of the disease.

Potential molecular mechanisms of Huanglian Jiedu Decoction in treatment of atherosclerosis based on network pharmacology / 中草药

Objective: To explore the potential molecular mechanism of Huanglian Jiedu Decoction in the treatment of atherosclerosis (AS) through pharmacology network. Methods: By identifying all the composition and effect targets of four herbal ingredients in Huanglian Jiedu Decoction from TCMSP platforms and literatures, and the pharmaceutical molecular-target network was constructed. The interaction network of drug-disease target by STRING platform was constructed by screening AS related targets through TTD, DrugBank and DisGeNET databases. The centre targets were analyzed by network topology. DAVID database was used to perform GO biological process analysis and KEGG pathway enrichment analysis of centre target proteins, and further construct a multi-dimensional network relationship diagram of the active component-AS target-KEGG pathway of Huanglian Jiedu Decoction. Results: A total of 71 active ingredients and 165 potential drug targets were obtained according to the screening conditions (OB ≥ 30%, DL ≥ 0.18) and accessing literatures. The main active ingredients in Huanglian Jiedu Decoction included sitosterol, quercetin, berberine, dehydrotanshinone IIA and neobaicalein, which could interfere with the formation of AS. A total of 175 disease targets were collected from the three disease databases under the search criteria of “atherosclerosis”. According to Degree, 223 centre target proteins of Huanglian Jiedu Decoction were screened, mainly invovling NOS2, NOS3, PTGS2, TNF, CYP2C9 and HMOX1, et al. GO biological process analysis identified 50 entries based on false discovery rate (FDR) ≤ 0.05, mainly including SRP-dependent targeting membrane transporters, nuclear-transcribed mRNA catabolic process, viral transcription, rRNA processing, translation and other bioanalysis process. The result of KEGG enrichment analysis showed 74 pathways were associated with AS, mainly involved in ribosome pathway, viral carcinogenesis pathway, cell cycle pathway, estrogen signaling pathway, et al. Conclusion: Huanglian Jiedu Decoction can treat AS through multi-ingredient, multi-target and multi-pathway interaction, which provides a theoretical basis for the clinical application of Huanglian Jiedu Decoction and the basic or clinical research of AS-related diseases. Meanwhile, it has a certain reference value for the research and development of new drugs and its application.

Preparation of self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase / 中草药

Objective: To prepare the self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase. Methods: M. haplocalyx oil was used as the oil phase, and C. tinctorius extract was used as the water phase. The prescription of self-microemulsion were optimized by pseudo-ternary phase diagram, the process and prescription of gel were screened by single-factor method and the appearance, viscosity and pH value were evaluated. Result: The optimal formulation of CTE-SMEDDS-BGs was as following: F68 was the emulsifier, anhydrous ethanol was the co-emulsifier, the Km ratio was 1:1, and the total amount of emulsifier and co-emulsifier to M. plocalyx oil was 8:2, carbopol-980 was 2%, glycerin was 6%, and C. tinctorius extract was 5 mL. The CTE-SMEDDS-BGs was obtained by adding the CTE-SMEDDS into swelling gel matrix and triethylamine was used to adjust the pH to 6.0. The characteristics of appearance were yellow translucent, moderate viscosity, uniform and delicate, non-greasy, and easy to spread on the skin, the viscosity was 4.98 × 104 mPa•s (RSD was 1.53%), pH was 6.04 (RSD was 0.44%). Conclusion: The CTE- SMEDDS-BGs with M. plocalyx oil as oil phase is simple and stable, and meets the requirements of gel topical preparations.