Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.

Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

Dens invaginatus (DI) is a developmental anomaly as a result of a deepening or invagination of the enamel organ into the dental papilla during tooth development. In addition, DI is a malformation with varying anatomical features, which poses numerous challenges to treatment. Endodontic treatment of dens in dente is one of the most complica-ted cases of DI. Herein, an immature lateral incisor that employed regenerative endodontic treatment was presented. The mentioned tooth was diagnosed with DI, pulp necrosis, and chronic apical periodontitis. Hence, a favorable prognosis has been shown by a 2-year review with cone beam computed tomography. The tooth was functional with normal periodontal parameters and exhibited a normal response to the electric pulp sensibility test. Thus, regenerative endodontic treatment can also be recommended to endodontists for teeth with DI.
Humans ; Regenerative Endodontics ; Incisor/diagnostic imaging* ; Dens in Dente ; Dental Pulp Necrosis/therapy* ; Odontogenesis

In reference with the systematic review of the thought of deqi (arrival of qi) put forward in Huangdi Neijing (Internal Classic of Yellow Emperor) and other classic books of traditional Chinese medicine, in view of detecting qi and identifying qi before treatment, as well as the prerequisites of deqi in tuina, meaning the accurate syndrome differentiation and manipulations, the importance of deqi in treatment with tuina is expounded. In association with clinical experience, the specific manifestations of deqi in patients during tuina are summarized, e.g. soreness, distention, pain, numbness, warm feeling and slight sweating, local changes in intestinal sound and skin color, as well as mind regulation. It is anticipated that deqi of tuina may be drawn the attention in clinical practice, and the relevant study be expanded.
Books ; Emotions ; Humans ; Medicine, Chinese Traditional ; Pain ; Qi

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

To systematically evaluate the clinical efficacy and safety of Ginkgo Leaf Tablets(GLT) in the treatment of acute cerebral infarction(ACI). Seven databases both at home and abroad were systematically retrieved from their establishment to March 2020. The data of the included studies were extracted after review and screening. The quality of the included studies was assessed with the Cochrane risk bias assessment tool, and then the included studies were put into Meta-analysis by RevMan 5.3 to evaluate the total cli-nical efficiency, neurological function score, blood lipids and incidence of adverse reactions in treatment of ACI by GLT. Finally, the GRADE system was adopted to evaluate the evidence quality of each outcome indicator and form recommendations. Ten studies involving 886 participants were included, all of which were of low quality. Meta-analysis results showed that,(1)in terms of the total clinical efficiency, GLT+Western medicine was superior to Western medicine alone(RR_(NDS)=1.20, 95%CI[1.06, 1.36], P=0.005; RR_(NIHSS)=1.35, 95%CI[1.09, 1.69], P=0.007), and there was no statistical difference between GLT+Xuesaitong Injection+Wes-tern medicine and Xuesaitong Injection+Western medicine(RR=1.16, 95%CI[1.00, 1.35], P=0.05).(2)In terms of improving neurological function score, GLT+Western medicine was superior to Western medicine alone(MD_(NIHSS[moderate(severe)])=-1.55, 95%CI[-2.22,-0.88], P<0.000 01; MD_(NIHSS(severe))=-7.51, 95%CI[-8.00,-7.02], P<0.000 01; MD_(NDS)=-1.36, 95%CI[-2.39,-0.33], P=0.01), and GLT+Danshen Injection+Western medicine was superior to Danshen Injection+Western medicine(MD_(NDS)=-3.09, 95%CI[-3.84,-2.34], P<0.000 01).(3)In terms of regulating blood lipids, GLT+Western medicine was superior to Wes-tern medicine alone(MD_(TC)=-1.40, 95%CI[-2.13,-0.66], P=0.000 2; MD_(TG)=-1.29, 95%CI[-1.86,-0.73], P<0.000 01; MD_(LDL-C)=-1.48, 95%CI[-2.91,-0.04], P=0.04; MD_(HDL-C)=0.07, 95%CI[0.02, 0.12], P=0.009).(4)In terms of incidence of adverse reactions, there was no statistical difference between GLT+Western medicine and Western medicine alone(RR=0.63, 95%CI[0.30, 1.32], P=0.22). The results of the evaluation showed that the evidence level of each outcome indicator was low, and the recommendation was at weak level. In conclusion, GLT+Western medicine could improve the total clinical efficiency, neurological function score, and blood lipid status, with a low incidence of adverse reactions. However, due to the small amount of included stu-dies, low study quality and low level of evidence, it is expected to carry out clinical studies with standardized design and large sample size in the future to further investigate the clinical efficacy and safety of GLT in the treatment of ACI.
Cerebral Infarction/drug therapy* ; Ginkgo biloba ; Humans ; Plant Leaves ; Tablets ; Treatment Outcome

Objective:This paper constructs a generalized regression neural network （GRNN） model to predict the disintegration time of traditional Chinese medicine （TCM） tablets. Method:Taking Astragali Radix as a model drug， the mixed Astragali Radix powders with different powder properties were prepared by mixing Astragali Radix extract powders with microcrystalline cellulose and lactose， which were made to Astragali Radix tablets by direct compression method. The powder properties of mixed Astragali Radix powders and the disintegration time of Astragali Radix tablets were determined， respectively. The correlation between the original data was eliminated by principal component analysis （PCA）. The principal component factors were used as the input layer of the GRNN model， and the disintegration time was used as the output layer for network training. Finally， the verification group data was used to predict the disintegration time， and the network prediction accuracy was calculated by comparing with the actual value. Result:Three principal component factors were obtained through PCA by analyzing the original nine variables that were correlated with each other （Hausner ratio， true density， tap density， compression degree， angle of repose， bulk density， porosity， water content and total dissolved solids）， which reduced the complexity of the network. The prediction value of the disintegration time based on this prediction method was in good agreement with the actual value， the error of disintegration time was 0.01-1.34 min and the average relative error was 3.16%. Conclusion:Based on the GRNN mathematical model， the physical properties of Astragali Radix extract powders can be used to accurately predict the disintegration time of Astragali Radix tablets， which provides a reference for studying the disintegration time of TCM tablets.

Objective:To explore the application effect of health education based on the information-motivation-behavioral (IMB) skills model in the health education of main caregivers of premature infants.Methods:A total of 200 premature infants and 200 primary caregivers admitted to Department of Neonatology in First Hospital of Qinhuangdao were selected as the research objects from January 2017 to December 2019. Using random number table method, they were divided into the control group and the observation group, with 100 premature infants and 100 caregivers in each group. The control group was given regular health education, while the observation group was given health education based on the IMB model skill on the basis of the control group. The growth and development of premature infants and their re-admission after discharge were compared between the two groups. The self-made Premature Infant Caregivers Care Knowledge Evaluation Form, Premature Infant Caregivers Care Ability Scale and Neonatology Satisfaction Questionnaire were used to evaluate the care knowledge, care ability and satisfaction of their caregivers.Results:The growth and development compliance rates of preterm infants in the two groups were respectively 86.00% and 74.00%, and the readmission rates after discharge were respectively 7.00% and 17.00%, and there were statistically significant differences between groups ( P<0.05) . After intervention, the scores of nursing knowledge, nursing ability and nursing satisfaction of caregivers in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The application of IMB model-based health education in caregivers of premature infants can improve the growth and development compliance rate of premature infants, reduce the re-admission rate after discharge, improve knowledge and ability of care of caregivers and improve satisfaction of caregivers.