Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

Objective To evaluate the clinical efficacy of invisible orthodontic appliances without brackets for the distal movement of maxillary molars to improve the ability of orthodontists to predict treatment outcomes.Methods Web of Science,Cochrane Library,Embase,PubMed,Wanfang Database,CNKI Database,and VIP Database were searched for studies investigating the efficacy of invisible orthodontic appliances for distal movement of maxillary molars in adult patients and published from database inception to August 1,2023.A total of three researchers screened the studies and evaluated their quality and conducted a meta-analysis of those that met quality standards.Results This study included 13 pre-and postcontrol trials with a total sample size of 281 patients.The meta-analysis revealed no sig-nificant differences in the sagittal or vertical parameters of the jawbone after treatment when compared with those before treatment(P＞0.05).The displacement of the first molar was MD=-2.34,95％CI(-2.83,-1.85);the displacement was MD=-0.95,95％CI(-1.34,-0.56);and the inclination was MD=-2.51,95％CI(-3.56,-1.46).There was a statistically significant difference in the change in sagittal,vertical,and axial tilt of the first molar before and after treatment.After treatment,the average adduction distance of the incisors was MD=-0.82,95％CI(-1.54,-0.09),and the decrease in lip inclination was MD=-1.61,95％CI(-2.86,-0.36);these values were significantly different from those before treat-ment(P＜0.05).Conclusion Invisible orthodontic appliances can effectively move the upper molars in a distal direc-tion and control the vertical position of the molars.When the molars move further away,there is some degree of com-pression and distal tilt movement,which is beneficial for patients with high angles.The sagittal movement of incisors is beneficial for improving the patient's profile.

Objective:To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening (ECS) panel with 216 diseases (216-ECS panel) within a Chinese population of childbearing age.Methods:Whole-exome sequencing data from a cohort of 3 097 unrelated healthy individuals (including 1 424 couples) from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed. Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis. The analysis included variant carrier rate, gene carrier rate, cumulative carrier rate, at-risk couple rates, and variant spectrum.Results:(1) Pathogenic variants were identified in 1 472 (47.53%, 1 472/3 097) individuals, with an average of 0.65 pathogenic variants per individual. The rate of at-risk couples was 3.93% (56/1 424). (2) A total of 180 genes were identified, with 16 genes exhibiting a gene carrier rate of ≥1% and 33 genes having a rate of ≥0.5%, most of which were associated with inherited metabolic diseases. Noteworthy genes with higher gene carrier rates and high-frequency variants included GJB2: c.235del, PAH: c.728G>A, ATP7B: c.2333G>T, SLC26A4: c.919-2A>G, GALC: c.1901T>C, POLG: c.2890C>T, SLC22A5: c.1472C>G, USH2A: c.2802T>G, SLC25A13: c.852_855del, GAA: c.761C>T and c.752C>T. Conclusion:This study offers a focused analysis of carrier frequencies and hot-spot variants of 216 diseases of the ECS panel constructed by our laboratory among the Chinese population, laying a foundation for the development of ECS programs tailored to the Chinese population.

Objective:To systematically evaluate the qualitative study on the sexual health needs of patients with ostomy based on theoretical domains framework (TDF), providing reference for clinical care and practice.Methods:A comprehensive search was conducted for qualitative studies on the sexual experience of ostomy patients in the China National Knowledge Infrastructure, Wanfang Data, VIP database, China Biology Medicine, PubMed, Embase, Web of Science, Cochrane Library, Elton B. Stephens Company (EBSCO), Elsevier Scopus (SCOPUS), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, with a timeframe of from the creation of the databases to April 15, 2024. The Joanna Briggs Institute Evidence Based Healthcare Center Critical Appraisal Tool was used to evaluate the quality of eligible literature, and the theoretical domain framework was used to integrate the extracted results.Results:A total of 11 articles were included and 51 results were extracted. Based on the theoretical framework, map the sexual health needs of ostomy patients to six core areas: knowledge, skills, optimism, outcome beliefs, environment and resources, and emotions.Conclusions:Medical staff should pay attention to the sexual health needs of patients with intestinal stomas. Based on the six core areas of knowledge, skills, optimism, outcome beliefs, environment and resources, and emotions, they should deeply explore the factors that affect their sexual health, provide professional guidance and comprehensive care, and improve their sexual health level and quality of life.

Objective: To investigate the level of maternal and infant health literacy and its influencing factors among lying-in women, so as to provide insights into formulating maternal and infant health education and promotion strategies. Methods: Lying-in women were sampled from Children's Hospital of Shanxi using a cluster sampling method from March to September 2022. Demographic characteristics, maternal and infant health literacy, and health education demands were collected through a questionnaire survey. Factors affecting maternal and infant health literacy among lying-in women were identified using a multivariable logistic regression model. Results: A total of 1 099 questionnaires were allocated, and 1 059 valid questionnaires were recovered, with an effective rate of 96.36%. Participants had a mean age of (30.93±4.01) years, 930 urban residents (87.82%), and 706 pluripara (66.67%). The overall prevalence of maternal and infant health literacy was 35.51% among lying-in women, and the prevalence rates of basic knowledge and concept, healthy lifestyles and behaviors and basic skills were 47.69%, 83.10% and 38.81%, respectively. Multivariable logistic regression analysis showed that educational level (diploma or undergraduate degree, OR=3.916, 95%CI: 1.250-9.031; master degree and above, OR=4.557, 95%CI: 1.498-11.460), occupation (company employees, OR=2.701, 95%CI: 1.385-5.268; medical staff, OR=2.981, 95%CI: 1.289-6.893), pluripara (OR=5.649, 95%CI: 3.919-8.142), participating in health education activities (OR=2.332, 95%CI: 1.524-3.570), and participating in schools for pregnant women (OR=2.252, 95%CI: 1.541-3.291) were promoting factors for maternal and infant health literacy; while gestational hypertension (OR=0.255, 95%CI: 0.133-0.488) and gestational diabetes (OR=0.318, 95%CI: 0.211-0.478) were inhibiting factors for maternal and infant health literacy. Most participants acquired health knowledge through online media (62.42%), and hoped to participate in health education activities through online media publicity (68.18%). Conclusions The maternal and infant health literacy level of lying-in women in this survey is associated with education, occupation, parturition frequency, participation in health education activities, participation in schools for pregnant women, gestational hypertension and gestational diabetes.

Objective:To analyze the value of shear wave elastography (SWE) in evaluating carotid artery elasticity in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD).Methods:A total of 98 T2DM patients diagnosed in the Second Affiliated Hospital of Dalian Medical University were selected and divided into three groups according to the results of liver ultrasound examination. 35 patients without NAFLD were in group A, 33 patients with mild NAFLD were in group B, and 30 patients with moderate to severe NAFLD were in group C. All selected individuals showed no plaque formation on carotid ultrasound examination. Left carotid artery intima-media thickness (IMT), carotid artery systolic diameter (Ds), carotid artery diastolic diameter (Dd), and peak systolic velocity (PSV) were measured using conventional two-dimensional and M-mode ultrasound. The stiffness coefficient (β) was obtained through calculation. SWE was used to measure the mean longitudinal modulus of elasticity (MEmean), mean minimum modulus of elasticity (MEmin), and mean maximum modulus of elasticity (MEmax) of the left carotid artery at the end of diastole.Results:There was no statistically significant difference in Ds, Dd, and PSV among the three groups (all P>0.05). Compared with group A and group B, group C had significantly higher IMT, β, MEmean, MEmax, and MEmin (all P<0.05). Compared with the group A, the group B had higher levels of MEmean, MEmax, and MEmin (all P<0.05), there was no statistically significant difference in IMT and β between the groups (all P>0.05). Correlation analysis showed that MEmax, MEmean, and MEmin in each group were positively correlated with β ( r=0.537, 0.543, 0.525, P<0.01), and also positively correlated with HbA 1c ( r=0.456, 0.483, 0.438, P<0.01), but not with IMT (all P>0.05). The intra observer Intraclass correlation coefficient (ICC) of MEmax, MEmean and MEmin measured by SWE was 0.847-0.887, and the inter observer ICC was 0.791-0.934, indicating a good repeatability. Conclusions:SWE can quantitatively evaluate the elasticity of the carotid artery in patients with T2DM and NAFLD.

OBJECTIVE To prepare Xiongzhi shigao decoction soluble microneedles， characterize it and investigate its transdermal properties in vitro. METHODS Two-step centrifugal method was used to prepare Xiongzhi shigao decoction soluble microneedles. The formability and mechanical property of the microneedles were evaluated from aspects of stroma fluidity， microneedle formability， needle hardness， etc. The appearance， mechanical strength， dissolution performance， skin barrier recovery performance and drug loading of the prepared microneedles were characterized by using active components of the soluble microneedle （chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide， isoimperatorin） as indicators. The in vitro transdermal performance was investigated by Franz diffusion cell. RESULTS The soluble microneedle tips of Xiongzhi shigao decoction prepared in this study were conical， evenly distributed and of the same thickness， with good mechanical properties； the tip of the needle could be almost completely dissolved after being penetrated into the skin of rats for 2 hours， and the skin barrier recovery performance was good； the drug loading of chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide and isoimperatorin were （87.04±1.12）， （67.69±1.23）， （20.65±0.17）， （35.00±0.11）， （153.83±0.21） and （23.52±0.50） μg per patch respectively. The results of in vitro transdermal study showed that cumulative release rates of 6 active components in this microneedle after 72 hours were 36.94%， 56.72%， 19.36%， 57.98%， 11.06% and 35.19%， respectively. CONCLUSIONS Xiongzhi shigao decoction soluble microneedles are prepared successfully in this study and have good formability， mechanical properties and pliable backing， which can significantly promote the transdermal drug delivery.

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
Animals ; Cell Differentiation/genetics* ; Chromatin/metabolism* ; Embryonic Stem Cells ; Germ Cells/metabolism* ; Germ Layers/metabolism* ; Mice

UNC-51-like kinase 1 (ULK1), as a serine/threonine kinase, is an autophagic initiator in mammals and a homologous protein of autophagy related protein (Atg) 1 in yeast and of UNC-51 in Caenorhabditis elegans. ULK1 is well-known for autophagy activation, which is evolutionarily conserved in protein transport and indispensable to maintain cell homeostasis. As the direct target of energy and nutrition-sensing kinase, ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological processes. Moreover, ULK1 has been widely reported to play a crucial role in human diseases, including cancer, neurodegenerative diseases, cardiovascular disease, and infections, and subsequently targeted small-molecule inhibitors or activators are also demonstrated. Interestingly, the non-autophagy function of ULK1 has been emerging, indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific contexts. Therefore, in this review, we summarized the structure and functions of ULK1 as an autophagic initiator, with a focus on some new approaches, and further elucidated the key roles of ULK1 in autophagy and non-autophagy. Additionally, we also discussed the relationships between ULK1 and human diseases, as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1, which will provide a clue on novel ULK1-targeted therapeutics in the future.