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.

At present,more and more scientific experiments are used in the research of traditional Chinese medicine(TCM),which promotes the elucidation of the effects of TCM.However,the real significance of scientific experiment lies in the discussion of the original theory,and in the guidance role in the original theory based on the discovery.Therefore,it will lose its real significance and value to only position scientific experiments as"explain"the mechanism of TCM effects rather than guiding the clarification and development of the principles of TCM.This paper analyzes the theoretical paradigms of modern science and TCM from the perspective of historical development,and theoretically discusses the due position and importance of scientific experiments in the theoretical research and development of TCM on their similarities and differences and their possible intersections.It holds that although scientific experiment and TCM belong to different theoretical paradigms,their objective materiality from clinical practice determines the interconnectedness between scientific experiment and TCM,that is,linking scientific experiment and TCM with the pathophysiological changes;In order to ensure the correctness of the connection between this scientific experiment and TCM,we should pay attention to the implementation of the scientific concept in scientific experiments to ensure the specificity of the research results,and finally making due contributions to the development of TCM theory.

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.

At present,more and more scientific experiments are used in the research of traditional Chinese medicine(TCM),which promotes the elucidation of the effects of TCM.However,the real significance of scientific experiment lies in the discussion of the original theory,and in the guidance role in the original theory based on the discovery.Therefore,it will lose its real significance and value to only position scientific experiments as"explain"the mechanism of TCM effects rather than guiding the clarification and development of the principles of TCM.This paper analyzes the theoretical paradigms of modern science and TCM from the perspective of historical development,and theoretically discusses the due position and importance of scientific experiments in the theoretical research and development of TCM on their similarities and differences and their possible intersections.It holds that although scientific experiment and TCM belong to different theoretical paradigms,their objective materiality from clinical practice determines the interconnectedness between scientific experiment and TCM,that is,linking scientific experiment and TCM with the pathophysiological changes;In order to ensure the correctness of the connection between this scientific experiment and TCM,we should pay attention to the implementation of the scientific concept in scientific experiments to ensure the specificity of the research results,and finally making due contributions to the development of TCM theory.

Purpose: Chronic low-grade inflammation is linked to the biology of aging; however, evidence supporting a causal relationship between periodontitis—a dysbiotic biofilminitiated inflammatory disease—and accelerated aging remains limited. This study investigated the causality between periodontitis and biological aging and identified potentially shared genomic loci, genes, and pathways. Methods: We conducted a 2-sample Mendelian randomization (MR) analysis to explore the causality of periodontitis on age acceleration measures (DNAm PhenoAge acceleration, GrimAge acceleration, Hannum age acceleration, and intrinsic epigenetic age acceleration) using a dataset from genome-wide association studies of European ancestry populations.Independent genetic variants associated with each trait were used as instrumental variables.The inverse variance-weighted (IVW) method served as the primary MR approach, supplemented by sensitivity testing. We also performed additional statistical genetic analyses to identify pleiotropic loci, shared functional genes, and potential biological pathways, integrating large-scale expression quantitative trait loci data from blood samples. Results: The MR analysis indicated a causal relationship between periodontitis and DNAm PhenoAge acceleration (IVW β=0.308; 95% confidence interval, 0.056–0.561; P=0.017), a finding corroborated by sensitivity analyses. There was a significant genetic overlap between periodontitis and age acceleration. Pleiotropic analysis revealed 24 shared SNPs associated with 242 genes, predominantly involved in immune functions and pathways related to cellular processes. Further integration analysis showed that 91 of these pleiotropic genes were causally linked to both conditions, with C6orf183 identified as a potential mediator. Conclusions This study presents compelling genetic evidence supporting a causal relationship between periodontitis and accelerated aging. Further research is required to validate these findings and investigate the underlying mechanisms.

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development.Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations.To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia,we examined patterns of dysmorphology caused by Hh signalling inhibition.Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 or 150 mg·kg-1 body weight at preselected time points between embryonic days (E)8.5 and 12.5.The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg·kg-1.Exposure between E9.5 and E10.5 induced frontal bone dysplasia,micrognathia and limb defects,with administration at E10.5 producing the most pronounced effects.This model showed decreased ossification of the frontal bone with downregulation of Hh signalling.The osteoid thickness of the frontal bone was significantly reduced.The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.

Objective Deletion detection and annotation of 18 lines from the population of specific chromosome 1 substitution strains ( PCSSs) derived from Chinese wild mice based on whole genome re-sequencing data. Methods Whole genome re?sequencing of the 18 lines were performed on the Illumina Hiseq platform. SpeedSeq software was used to detect the deletion after read alignment. Further annotation was obtained using SnpEff software. Results 13803 dele?tions were identified among the 18 lines, the length of deletion was ranged from 51bp to 70 kb, among them nearly 50%were less than 500 bp. Through functional annotation,we found most of the variants were located in intronic (50. 361%) and intergenic (28. 745%) regions. However, we also identified 31 protein coding genes harboring loss?of?function dele?tions. Among them, 3 genes were associated with human diseases, 7 genes were participated in 11 KEGG pathways. Conclusion The chromosome 1 of PCSSs harbors abundant deletion mutations which can be used as genetic markers in genetic studies.

Objective To investigate the influence of experimental scotoma on multifocal visual evoked potential (mf-VEP). Methods The mf-VEP of 10 healthy individuals (20 eyes) was measured with VERIS Science 4.0. Every eye was measured for 3 times. The right eye was measured with full field stimulation and upper hemi-field or lower hemi-field masked. The left eye was measured with full field stimulation and central three-rings area or lower nasal field masked. The first slice responses of the second order in different field were analyzed and compared by VERIS software. Results The mf-VEP in masked area was undetectable or obviously decreased in all subjects. In most unmasked field, the amplitudes of mf-VEP were not changed, except that in some place decreased slightly with statistically significant difference in comparison to the full field stimulation mode. Conclusion mf-VEP is influenced with experimental scotoma. The mf-VEP changes are consistent with the visual field masked.

Objective To investigate the characteristics of multifocal visual evoked potential (mf-VEP) in healthy individuals, and provide normal reference values for its clinical application. Methods The mf-VEP of 37 healthy individuals (70 eyes) were examined by VERIS Science TM 4.0. The visual stimulus was a dart board with patterns consisted of 60 patches spanning a 25? visual field. The length of m-sequence was 2 14-1. The results were recorded by bipolar occipital straddle. The signal was amplified 100 K and was put through a band-pass filter between 3 and 100 Hz. The first slice of the second order kernel was analyzed by VERIS software. The summed responses of fields with different stimulus were analyzed and compared according to different ages, genders and eyes. Results The latencies and response densities of amplitude had statistically significant differences both in dimidiate and quartered field(P 0.05). Conclusions The mf-VEP of healthy individuals can reflect the VEP at different field locations objectively with its specific physiological characteristics, which may provide normal reference values for its clinical application.