ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

Objective To observe the effects of abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on balance,walking function and trunk control in patients recovering from stroke.Methods Seventy-eight patients recovering from stroke were randomly divided into an observation group and a control group,with 39 patients in each group.The control group was given conventional rehabilitation exercises,while the observation group was given abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on the basis of the control group.Both groups were treated for 2 consecutive months.After 2 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Berg Scale score and the Timed Up and Go Test(TUGT)were observed before and after treatment.The changes in the National Institutes of Health Stroke Scale(NIHSS)scores were compared before and after treatment between the two groups.The Sheikh Trunk Control Scale scores were also evaluated.Results(1)The total effective rate of the observation group was 94.87%(37/39),and the total effective rate of the control group was 80.00%(31/39),and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the Berg scores of the patients in the two groups were significantly increased(P＜0.05),and the Berg scores of the observation group were higher than those of the control group,and the difference was statistically significant(P＜0.05).(3)After treatment,the TUGT time and NIHSS score of patients in the two groups were significantly improved(P＜0.05),and the TUGT time of the observation group was shorter than that of the control group,and the NIHSS score was lower than that of the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the Sheikh trunk control scores of the two groups were significantly increased(P＜0.05),and the Sheikh trunk control score of the observation group was higher than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Abdominal penetrating moxibustion method combined with acupuncture at the four chong points for the treatment of stroke recovery can effectively restore the patients'balance and walking function,improve the patients'trunk control ability,and the therapeutic effect is precise.

Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.

Objective To construct a lentiviral vector for overexpression of bone morphogenetic protein 7(BMP7)in mice,and the effect of BMP7 overexpression on the expression of Jagged1 in mouse aortic endothelial cells and the calcification of the co-cultured vascular smooth muscle cells(VSMCs)were analyzed.Methods According to the target gene information Mouse-BMP7(NM_007557.3)and plasmid information pLVX-zsGreen-C1,gene sequence synthesis was carried out to construct BMP7 overexpression lentivirus.The efficiency of BMP7 overexpression lentivirus infection was detected by qPCR;the expression of Jagged1 protein in aortic endothelial cells from infected mice was detected by Western blot.The endothelial cells with lentivirus overexpressing BMP7 were co-cultured with VSMCs,and the calcification of VSMCs was observed by alizarin red staining.Results BMP7 overexpression lentiviral vector was successfully constructed and transfected into aortic endothelial cells.qPCR test results showed that the expression level of BMP7 mRNA was significantly increased in the BMP7 overexpression group than that in the normal control group(P<0.01),while there was no significant difference in the expression of BMP7 mRNA between the empty vector control group and the normal control group(P>0.05).Western blot results showed that the expression level of Jagged1 protein in endothelial cells of mouse in the BMP7 overexpression group was significantly lower than that in the normal control group(P<0.01),while there was no significant difference in the expression level of Jagged1 protein in endothelial cells between the empty vector control group and the normal control group(P>0.05).The results of alizarin red staining showed that the calcification of VSMCs was significantly increased after co-cultured with endothelial cells infected with BMP7 lentivirus.Conclusion Mouse BMP7 overexpression lentiviral vector was successfully constructed,and overexpression of BMP7 can reduce the expression of Jagged1 in mouse aortic endothelial cells and promote the calcification of co-cultured VSMCs.

Objective The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.Methods We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg·day) and 50 μg/(kg·day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing. Results Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment. Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.

Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1％formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62％-101.24％.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

For the past 30 years,percutaneous balloon mitral valve dilatation has been performed under the guidance of X-rays and bedside ultrasound.However,there are still some cases of mitral valve stenosis in the large atrium where balloon dilation failed.Intraperitoneal ultrasound-guided percutaneous balloon mitral valve plasty is accurate and feasible,which can reduce the occurrence of complications and improve the success rate of such elderly complex cases.Two patients with severe mitral stenosis underwent percutaneous balloon mitral valve plasty guided by intracardiac ultrasound.The operations were successful without any complications,which can provide reference for clinical treatment of mitral stenosis.

Objective:To investigate the expression pattern and prognostic value of NUF2(Ndc80 kinetochore complex component)in breast cancer(BC).Methods:In the present study,the trancriptional level and survival information of NUF2 was analyzed by ONCOMINE dataset,bc-GenExMiner,Kaplan-Meier Plotter and TCGA.Results:NUF2 was highly expressed in BC com-pared with normal samples(P＜0.05).In addition,the BC patients younger than 51 years old(P＜0.0001),nodal metastasis(P=0.0168),with basal-like BC(P＜0.0001),orestrogen receptor(ER)-negative(P＜0.0001),progesterone receptor(PR)-negative(P＜0.0001),human epidermal growth factor receptor-2(HER2)-positive(P＜0.0001)and triple-negative BC(P＜0.0001)pathological clas-sification have a higher transcriptional level of NUF2.Survival analysis indicated that patients with low expression level of NUF2 have a better relapse-free survival(RFS,HR=1.63,P＜0.0001).Fur-ther anaysis revealed that the NUF2 expression was negatively related to the RFS of BC patients with ER-positive or PR-positive or HER2-negative pathological classification(HR=2.40,P=0.0015).Conclusion:NUF2 play an important role in BC and can be a potential prognostic bio-marker for ER-positive or PR-positive or HER2-negative BC patients.