ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVES: To analyze the potential causal relationship between gut microbiota and food allergy (FA) using two-sample Mendelian randomization (MR) methods. METHODS: Data from genome-wide association studies on gut microbiota and FA were utilized. MR analysis was conducted employing inverse variance weighting, MR-Egger regression, and weighted median methods to assess the causal relationship between gut microbiota and FA. Cochrane's Q test was used to evaluate heterogeneity of instrumental variables, MR-PRESSO analysis was conducted to test for outliers and pleiotropy, and MR-Egger regression was employed to assess horizontal pleiotropy. The "leave-one-out" method was used to evaluate the impact of removing individual single nucleotide polymorphisms on the causal relationship. RESULTS: Inverse variance weighting analysis revealed that the phylum Verrucomicrobia, family Verrucomicrobiaceae, order Verrucomicrobiales, genus Ruminococcaceae UCG013, and genus Akkermansia were negatively associated with FA (P<0.05). Sensitivity analyses confirmed the reliability of the findings, indicating no heterogeneity or pleiotropy present. CONCLUSIONS There is a causal relationship between gut microbiota and FA, with Verrucomicrobia, Verrucomicrobiaceae, Verrucomicrobiales, Ruminococcaceae UCG013, and Akkermansia potentially reducing the risk of developing FA. These findings provide potential targets for the treatment and prevention of FA; however, further research is needed to explore the specific mechanisms by which the microbiota influence FA.
Humans ; Mendelian Randomization Analysis ; Gastrointestinal Microbiome ; Food Hypersensitivity/microbiology* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

Risks of food safety induced by small molecule drug residues in animal food and environment have become an increasing public concern,so it is necessary to develop highly sensitive and easy-to-operate techniques to detect small molecules.Herein,a metasurface plasma resonance(MetaSPR)sensor chip coupled with gold nanoparticles(AuNPs)was developed for detection of enrofloxacin(ENR)based on competitive immunoassay.The detection range of the sensor for ENR was 0.025-3.2 ng/mL,and the detection limit(3σ)was 20 pg/mL.The biosensor showed excellent performance including high selectivity,good stability,ease to operate and high throughput,etc.The developed method was applied to detection of ENR residues in real samples,with recoveies of 96.0% -105.0%.The proposed sensing strategy provided new technique reference for detection of other small molecules in the field of residue analysis in food safety and environment monitoring.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

Objective:Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF.Results:The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), P<0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), P<0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank P=0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank P=0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI ( HR=1.34, 95% CI: 1.01-1.79, P=0.043). Conclusion:Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.