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.

Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the char-acteristics 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 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 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.

OBJECTIVE: To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD). METHODS: Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq). RESULTS: The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23⁺⁴ weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq. CONCLUSION T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.
Female ; Humans ; Pregnancy ; Amniocentesis ; Chromosomes, Human, Pair 2/genetics* ; DNA Copy Number Variations ; Fetal Death ; Fetal Growth Retardation/genetics* ; Fetus ; Mosaicism ; Oligohydramnios ; Placenta ; Trisomy/genetics* ; Uniparental Disomy/genetics*

Recent advances in genome editing, especially CRISPR-Cas nucleases, have revolutionized both laboratory research and clinical therapeutics. CRISPR-Cas nucleases, together with the DNA damage repair pathway in cells, enable both genetic diversification by classical non-homologous end joining (c-NHEJ) and precise genome modification by homology-based repair (HBR). Genome editing in zygotes is a convenient way to edit the germline, paving the way for animal disease model generation, as well as human embryo genome editing therapy for some life-threatening and incurable diseases. HBR efficiency is highly dependent on the DNA donor that is utilized as a repair template. Here, we review recent progress in improving CRISPR-Cas nuclease-induced HBR in mammalian embryos by designing a suitable DNA donor. Moreover, we want to provide a guide for producing animal disease models and correcting genetic mutations through CRISPR-Cas nuclease-induced HBR in mammalian embryos. Finally, we discuss recent developments in precise genome-modification technology based on the CRISPR-Cas system.
Animals ; CRISPR-Cas Systems/genetics* ; DNA/genetics* ; Embryo, Mammalian/metabolism* ; Endonucleases/metabolism* ; Gene Editing ; Mammals/metabolism*

To evaluate the psychological symptoms of patients with Crohn disease (CD), and to explore the risk factors affecting quality of life (QOL) in CD patients, 50 adult patients with CD, and 50 healthy controls were enrolled. Psychological questionnaires including self-rating anxiety scale (SAS), self-rating depression scale (SDS), the inflammatory bowel disease questionnaire (IBDQ) and the short form-36 health survey (SF-36) were completed. The results showed both the SAS (40.3±8.5 VS 37.6±7.0) and the SDS (47.1±11.1 VS 41.8±9.6) in CD patients were significantly higher than those in the healthy controls ( t=5.4, P<0.05; t=10.6, P<0.05). The IBDQ scores revealed the physical symptoms scores were 49.50±7.62, systemic symptoms scores 23.92±5.07, emotional functions scores 57.13±15.62, and social function scores 22.15±9.08 in CD active phase. However, the above scores were 60.12±4.01, 26.24±3.97, 67.34±15.17, and 25.44±2.03 respectively in the remission phase. Four subscale items of IBDQ in CD active phase were significant lower than those in the remission phase (all P<0.05). The subscale items of SF-36 scores (PF, RP, BP, GH, VT, SF, RE, MH) in CD patients were significant lower than those in healthy controls (all P<0.05). The SF-36 items scores of PF,RP and MH in the remission phase were significant higher than those in the active phase (all P<0.05). The SF-36 items scores of GH and VT in patients with malnutrition were significant lower than those with nutrition (both P<0.05). Multivariate regression analysis showed that disease status and nutritional risk ( P<0.05) significantly affected the patients' IBDQ scores. Factors including sex, age, marital status, education background, medical insurance, use of biologicals, surgery treatment had little influence on the total score of IBDQ ( P>0.05). Psychological conseling and treatment in the active phase may improve QOL of CD patients.

AlM: To analyze the prescribing of different antiplatelet drugs and clinical conditions of patients with coronary heart disease in department of Geriatrics. METHODS: This study was a single center and cross-sectional study. Patients with coronary heart disease were recruited when hospitalized in the department of Geriatrics department, Xiangya Hospital, Central South University between December 2021 and June 2022. We investigated and analyzed the clinical conditions of patients including the prescribing of the antiplatelet drugs. RESULTS: A total of 347 coronary heart disease patients with a mean age of (65.2 ± 10.1) years were included. The antiplatelet drug clopidogrel was the most commonly prescribed. Among the different dual antiplatelet therapy (DAPT), aspirin combined with clopidogrel was the most widely used. With the increasing of the numbers of target coronary lesions, the prescribing rate of clopidogrel increased significantly (P < 0.05). In three groups with different degrees of target coronary lesions, the prescribing rate of aspirin was higher than that of indobufene (P < 0.05). Compared with patients taking aspirin, the patients taking indobufene were older with a higher blood creatinine level, a higher proportion of chronic gastropathy and the higher level of platelet aggregation rates (P < 0.05). CONCLUSlON: Clopidogrel is the most commonly prescribed antiplatelet drugs in patients with coronary heart disease. Aspirin combined with clopidogrel is the most widely used in DAPT. Compared with aspirin, indobufene is more commonly used in elderly patients with the chronic gastritis and a higher serum creatinine level.

Objective: To investigate the impact of maternal X chromosome aneuploidies on cell free DNA (cf-DNA) prenatal screening. Methods: After genetic counseling, invasive prenatal diagnosis was provided for the 124 cases with high risk of sex chromosome aneuploidie (SCA) indicated by cf-DNA prenatal screening. For cases with discordant results of fetal prenatal diagnosis and cf-DNA prenatal screening, maternal leukocyte was collected for copy number variation sequencing (CNV-seq) to detect whether the maternal X chromosome was carrying variations. Results: Totally, 124 cases with high risks of SCA indicated by cf-DNA prenatal screening, 9 cases refused to take invasive prenatal diagnosis, while the remaining 115 cases received. Among the 115 cases, 41 cases received accordant results with cf-DNA prenatal screening while 74 cases discordant. Among the 74 cases with discordant results, 19 cases were indicated with maternal X chromosome variations by maternal leukocyte CNV-seq, which accounting for 25.7% (19/74) of the SCA false positive cases, and 15.3% (19/124) of all SCA cases. Conclusions Pregnant women with X chromosome variations may affect the results of cf-DNA prenatal screening, resulting in false positive or false negative outcomes, it should be emphasized that the cf-DNA results may be affected by maternal X chromosome variations. In cases with discordant results of prenatal diagnosis and cf-DNA prenatal screening, maternal leukocyte CNV-seq is recommended to find the reasons of false positive or negative results. And cf-DNA prenatal screening is not recommended for pregnant women who are already known with X chromosome variations.