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.

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

Objective To identify inflammation-related genes in atrial fibrillation(AF)and explore the possible role and mechanism of these genes and infiltrating immune cells in the development of AF.Methods A series of bioinformatics analysis combined with machine learning algorithms to identify biomarkers of AF,the receiver operating characteristic(ROC)curves were used to verify the prediction and diagnostic value of key genes,and Spearman correlation analysis was used to clarify the correlation between key genes and infiltrating immune cells.Results 593 differential genes(| log2(fold change,FC)|>1,P<0.05),7 immune cell subtypes(P<0.05)were selected,190 immune-related differential genes were obtained,3 biomarkers(IGF1,PTGS 2 and PPARG),and the correlation analysis showed that 3 markers were significantly associated with infiltrating immune cells(P<0.05).Conclusion IGF1,PTGS2 and PPARG are inflammation-related genes of AF,which are speculated to be closely related to the process and pathway of immune cell infiltration.

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.

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

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.

Glucagon⁃like peptide⁃2 (GLP⁃2) is a peptide hormone secreted by L cells in the gut. GLP⁃2 plays an important role in anti⁃inflammation, promoting proliferation and repair, and promoting nutrient absorption through various signaling pathways in the gastrointestinal tract. Long ⁃ acting analogs of GLP ⁃ 2 have been used in the treatment of short bowel syndrome and Crohn’s disease, but using GLP⁃2 also has the risk of promoting tumorigenesis. This article introduces GLP ⁃ 2 and its physiological role in gastrointestinal tract, and expounds the possible mechanism of GLP ⁃ 2 related to tumorigenesis and the tumorigenesis risk of endogenous and exogenous GLP⁃2 therapy.

Objective To investigate the prenatal diagnosis and genetic counseling of fetal nuchal fold (NF) thickening.Methods This study retrospectively analyzed 17 fetuses with increased NF detected by prenatal ultrasound examination in Peking Union Medical College Hospital,Peking Union Medical College & Chinese Academy of Medical Sciences from December 1,2016 to December 1,2017.All cases were divided into isolated (isolated group) or non-isolated increased NF group (non-isolated group) according to whether the fetus had concomitant ultrasonographic abnormalities or not.Karyotype and chromosomal microarray analysis (CMA) were performed on all cases.Clinical data,prenatal genetic testing results and pregnancy outcomes were analyzed.Results Of those twelve cases in the isolated group,two were terminated due to the identification of chromosomal abnormalities and pathogenic copy number variations (CNVs) and the fetal autopsy results were consistent with the prenatal diagnosis.The rest 10 pregnancies were all continued including one fetus carrying a variant of unknown significance,which was proved to be a paternal heredity by CMA,and nine without genetic abnormalities and all-these infants were healthy during follow-up.Among the five non-isolated cases,one was diagnosed as trisomy 21 by karyotyping and CMA,and the other four were found to have structural abnormalities under ultrasound scan,but without genetic abnormalities in karyotyping and CMA.And all the five pregnancies were terminated after genetic counseling and three of them chose whole exome sequencing (WES) for further test.One homozygous mutation in CHRNA 1 gene and one de novo mutation in SETD2 gene were found in two cases,respectively,while no abnormality was identified in the other one case.Conclusions Once increased NF were indicated by ultrasound examination,prenatal genetic testing should be offered to the patients,including CMA,regardless of other ultrasonographic abnormalities,and WES should also be offered when necessary.Considering a thickened NF is associated with increased risks of structural defects,a close follow-up with fetal echocardiography and ultrasound is required even the prenatal tests are normal.

OBJECTIVE:To establish a method for simultaneous determination of ephedrine hydrochloride,nitrofural and di-phenhydramine hydrochloride in Compound diphenhydramine nasal drop. METHODS:RP-HPLC method was adopted. The determi-nation was performed on Inertsil ODS-3 C18 column with mobile phase consisted of 0.05 mol/L potassium dihydrogen phosphate buf-fer(pH 7.0)-acetonitrile(gradient elution)with flow rate of 1.0 mL/min. The detection wavelength was set at 256 nm,and the col-umn temperature was 35 ℃. The sample size was 20 μL. RESULTS:The concentrations of phedrine hydrochloride,nitrofural and diphenhydramine hydrochloride ranged 122.1-366.3 μg/mL(r=0.9999),5.2-15.5 μg/mL(r=0.9998)and 31.5-94.5 μg/mL(r=0.9994),respectively. The limits of quantitation were 2.442,0.010,2.520 μg/mL,and the limits of detection were 0.810,0.003, 0.830 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were lower than 1.0%. The recoveries of them were 99.2%-101.7%(RSD=0.9%,n=9),96.4%-102.0%%(RSD=1.7%,n=9),100.2%-101.9%(RSD=0.4%,n=9),respec-tively. CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for simultaneous determination of ephedrine hydrochloride,nitrofural and diphenhydramine hydrochloride in Compound diphenhydramine nasal drop.

·AIM: To investigate the clinical efficacy of intravitreal injection of Ranibizumab and 577nm laser in the treatment of retinal vein occlusion combined with macular edema.·METHODS: Totally 64 patients ( 64 eyes ) with retinal vein occlusion accompanied by macular edema were treated in our hospital from June 2014 to March 2017. Among them, 40 cases ( 40 eyes ) were in the central retinal vein occlusion group, 24 cases (24 eyes) were in the branch retinal vein occlusion group. They were treated with intravitreal injection of ranibizumab 0. 5mg, and the laser photocoagulation of 577nm was performed at 5 to 7d after injection. Meanwhile, 42 patients who did not wish to be treated with injection were treated with laser treatment only. The changes of the indexes before and after treatment were compared.·RESULTS: The average number of blocking group repeated injection of branch retinal vein for 1. 71 ± 0. 79, while the average number of patients with repeated injection of central retinal vein occlusion was 2. 11 ± 0. 80. All patients requiring repeated injections interval was greater than 30d. At 1mo after treatment, there was no patients with decreased visual acuity in branch retinal vein occlusion group, while there were 6 eyes with that in central retinal vein occlusion group, 14 eyes in simply laser group. The mean best corrected visual acuity (LogMAR) of the three groups was 0. 87±0. 60, 0. 57±0. 48 and 0. 54±0. 32, respectively, were significantly lower than that before treatment (1.26±0.53, 0.86±0.39, 0.76±0.26;P< 0. 05 ). The mean macular retinal thickness before treatment was 683.24±211.83, 557.39±128.29 and 545.82± 129. 76μm, were significantly higher than those at the last follow-up 412. 09±257. 38, 356. 29 ± 133. 02 and 322. 78 ± 109. 55μm ( P < 0. 05 ). There were 6 cases of subconjunctival hemorrhage in patients treated with laser therapy combined with laser therapy. The intraocular pressure increased to 25mmHg in 2 eyes in 2 patients and recovered after symptomatic treatment.· CONCLUSION: Intravitreal injection of ranibizumab combined with 577nm laser treatment can greatly enhance the visual acuity, effective decrease macular retinal thickness in patients with retinal vein occlusion and macular edema.