This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Cytochrome P450 family 3 subfamily A(CYP3A),a major member of cytochrome P450(CYP)family,is one of the most important drug metabolizing enzymes in human.CYP3A includes 4 gene subtypes(CYP3A4,CYP3A5,CYP3A7,and CYP3A43),which is involved in 60%of drug metabolism in the human.It is not only widely distributed in normal tissues,but also significantly overexpressed in various tumor tissues.Recently,CYP3A has attracted great attention due to its involvement in the progression from chronic atrophic gastritis to gastric cancer,as well as the differential metabolism and resistance of chemotherapeutic drugs.Targeting CYP3A gene mediated-prodrug provides new ideas for the treatment of gastric cancer and is expected to become a new target for the diagnosis and treatment of gastric cancer.

To study the characteristics of heart rate rhythm in pregnant women at different trimester of pregnancy, and to explore the relationship between the basic rhythm of heart rate and pregnancy complications. Thirteen pregnant women who were diagnosed with normal early pregnancy in the Reproductive Center of the Second Affiliated Hospital of Soochow University from June 2018 to December 2019 were prospectively selected. Personal files were created and the heart rate data of pregnancy women was collected 24 hours a day by wearable devices until delivery. Prenatal examination and pregnancy outcomes were surveyed at follow-up. The cosine analysis method and the designed statistical module were used to analyze the long-term rhythm of pregnant women's heart rate. The heart rate of pregnant women showed a significant rhythm at different gestational weeks. Compared with the gestational week of 12, the midline-estimating statistic of rhythm(MESOR) increased significantly at the gestational week of 28 and 32 (t=-2.751,P=0.013;t=-2.314,P=0.032).The phase of rhythm shifted from 14∶00 pm in the first trimester of pregnancy (12 weeks) to 16∶00 pm in the second trimester (24 weeks) (t=2.613,P=0.018) and returned to 14∶00 pm at the third trimester (32 weeks) (t=-2.176,P=0.046). Season had no significant effect on the changes of MESOR, amplitude and phase of maternal heart rate in the first trimester (t=-0.356,P=0.729;t=-0.777,P=0.464;t=-0.434,P=0.673), while season had no significant effect on the changes of MESOR, amplitude and phase in the third trimester (t=-0.663,P=0.532;t=-0.209,P=0.841;t=0.625,P=0.592). The heart rate of one pregnant woman with natural delivery had rhythm disorder from the start of labor to delivery. The heart rate of one pregnant woman with premature rupture of membranes showed rhythm disorder before and after the rupture of membranes, and smaller amplitude. Rhythm disturbance may play a suggestive role in preterm delivery and labor initiation. In conclusion, pregnancy may cause changes in the internal heart rate rhythm. Maternal internal rhythm disturbance may occur when delivery or premature rupture of membranes occurs. The heart rate rhythm of pregnant women may be related to some common complications of pregnancy such as premature rupture of membranes.
Infant, Newborn ; Pregnancy ; Female ; Humans ; Fetal Membranes, Premature Rupture ; Pregnancy Outcome ; Pregnancy Complications ; Pregnancy Trimester, Third ; Premature Birth ; Periodicity

To study the characteristics of heart rate rhythm in pregnant women at different trimester of pregnancy, and to explore the relationship between the basic rhythm of heart rate and pregnancy complications. Thirteen pregnant women who were diagnosed with normal early pregnancy in the Reproductive Center of the Second Affiliated Hospital of Soochow University from June 2018 to December 2019 were prospectively selected. Personal files were created and the heart rate data of pregnancy women was collected 24 hours a day by wearable devices until delivery. Prenatal examination and pregnancy outcomes were surveyed at follow-up. The cosine analysis method and the designed statistical module were used to analyze the long-term rhythm of pregnant women's heart rate. The heart rate of pregnant women showed a significant rhythm at different gestational weeks. Compared with the gestational week of 12, the midline-estimating statistic of rhythm(MESOR) increased significantly at the gestational week of 28 and 32 (t=-2.751,P=0.013;t=-2.314,P=0.032).The phase of rhythm shifted from 14∶00 pm in the first trimester of pregnancy (12 weeks) to 16∶00 pm in the second trimester (24 weeks) (t=2.613,P=0.018) and returned to 14∶00 pm at the third trimester (32 weeks) (t=-2.176,P=0.046). Season had no significant effect on the changes of MESOR, amplitude and phase of maternal heart rate in the first trimester (t=-0.356,P=0.729;t=-0.777,P=0.464;t=-0.434,P=0.673), while season had no significant effect on the changes of MESOR, amplitude and phase in the third trimester (t=-0.663,P=0.532;t=-0.209,P=0.841;t=0.625,P=0.592). The heart rate of one pregnant woman with natural delivery had rhythm disorder from the start of labor to delivery. The heart rate of one pregnant woman with premature rupture of membranes showed rhythm disorder before and after the rupture of membranes, and smaller amplitude. Rhythm disturbance may play a suggestive role in preterm delivery and labor initiation. In conclusion, pregnancy may cause changes in the internal heart rate rhythm. Maternal internal rhythm disturbance may occur when delivery or premature rupture of membranes occurs. The heart rate rhythm of pregnant women may be related to some common complications of pregnancy such as premature rupture of membranes.
Infant, Newborn ; Pregnancy ; Female ; Humans ; Fetal Membranes, Premature Rupture ; Pregnancy Outcome ; Pregnancy Complications ; Pregnancy Trimester, Third ; Premature Birth ; Periodicity