Breast cancer is a kind of malignant tumor with a complex mechanism， and its morbidity and mortality are increasing year by year， which seriously threatens women's health. At present， the main clinical treatments are surgical resection， radiotherapy， chemotherapy， and drug therapy， but they are often accompanied by side effects and adverse reactions， which affect the therapeutic effect. Traditional Chinese medicine （TCM） has the advantages of multi-component and multi-target treatment in the fight against breast cancer. The wnt/β-catenin signaling pathway is one of the classic pathways in cancer research. Abnormally activated Wnt/β-catenin signaling pathway inhibits β-catenin degradation by blocking the formation of Axin/glycogen synthase kinase 3β/adenomatous polyposis coli complex， thus promoting β-catenin nuclear metastasis， and it binds to T cell transcription factor/lymphoenhancer factor-1 to initiate downstream target genes and further interfere with the proliferation， migration， and invasion of tumor cells to affect the tumor process. Previous studies have shown that TCM monomers and compounds can mediate the Wnt/β-catenin signaling pathway to inhibit the malignant phenotype of breast cancer cells， thus playing an anti-breast cancer role， and the biochemical process involved in the regulation of therapeutic drugs has not been systematically combed. By analyzing and collating Chinese and foreign literature at the present stage， this paper discussed the association mechanism between Wnt/β-catenin signaling pathway and breast cancer and analyzed the internal mechanism of TCM monomers and compounds in mediating Wnt/β-catenin signaling pathway to exert anti-breast cancer effect. The statistical results showed that the flavonoids， alkaloids， and terpenoids in TCM monomers could target the Wnt/β-catenin signaling pathway and block the further development of malignant phenotype of breast cancer cells. TCM compounds with functions of clearing heat and detoxifying， promoting blood circulation and removing blood stasis， and tonifying kidney and liver were commonly used to intervene in the Wnt/β-catenin signaling pathway to prevent breast cancer. Compared with the current inhibitors of Wnt/β-catenin signaling pathway， the application of TCM monomers and compounds is expected to bring low-toxicity and high-efficiency breast cancer treatment drugs to the clinical practice， and the existing results provide a reference for the subsequent screening， research， and development of TCM small-molecule compounds and TCM compounds against breast cancer.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Mesenchymal stem cells (MSCs) are an effective therapeutic strategy to delay aging in dogs, they are prone to aging and have poor genetic stability when cultured for a long time in vitro. Therefore, it is of great significance to explore a method to improve the anti-aging ability of MSCs. Previous studies have shown that sirtuin 6 (SIRT6) plays an important role in anti-aging. This study constructed MSCs with overexpressed SIRT6 gene. Through Giemsa staining and senescence-associated β-galactosidase staining, it was found that SIRT6 significantly enhances the anti-aging capacity of MSCs. Transmission electron microscopy imaging and the detection of oxidative stress-related indicators revealed that SIRT6 improves the anti-aging capacity of MSCs by maintaining mitochondrial homeostasis and reducing oxidative stress levels. Transcriptome sequencing analysis revealed that SIRT6 mainly acted on phosphatidylinositol-3-kinase, mitogen-activated protein kinase and other aging and inflammation related pathways. In the establishment and verification of aging models in mice and dogs, it was found that the spatial memory ability of the model mice was significantly increased after intravenous transplantation of SIRT6 overexpression cells, the organ index was also significantly changed, and the anti-oxidative capacity of the dogs and mice blood was improved. The morphology of the spleens and livers in the SIRT6 overexpression cell treatment group could be effectively restored, and the expression levels of aging and inflammation-related proteins were significantly decreased. This study provides a new idea for the study of SIRT6-mediated anti-aging of MSCs.
Animals ; Dogs ; Mesenchymal Stem Cells/metabolism* ; Sirtuins/genetics* ; Aging/physiology* ; Mice ; Oxidative Stress ; Mesenchymal Stem Cell Transplantation

Objective:To compare the effects of enhanced heat preservation strategies and conventional heat preservation strategies in the operation room on body temperature, coagulation function, and myocardial injury in patients with cervical spinal cord injuries.Methods:A retrospective cohort study was conducted to analyze the clinical data of 160 patients with cervical spinal cord injuries admitted to Second Affiliated Hospital of Xi′an Jiaotong University and Affiliated Honghui Hospital of Xi′an Jiaotong University from February to October 2022, including 82 males and 78 females, aged 38-64 years [(50.6±8.7)years]. Injured segments included C 3 in 19 patients, C 4 in 33, C 5 in 39, C 6 in 38, and C 7 in 31. According to American Spinal Injury Association (ASIA) classification, 10 patients were classified into grade A, 83 grade B, 39 grade C, and 28 grade D. All the patients underwent cervical laminoplasty, decompression and bone graft fusion surgery. According to different heat preservation strategies intraoperatively, the patients were divided into conventional heat preservation group ( n=80) and enhanced heat preservation group ( n=80). The body temperature changes before surgery, at 2 hours during surgery, immediately after surgery, at 2 and 24 hours after surgery were compared between the two groups. The changes of coagulation function before surgery and at 4 hours after surgery were compared between the two groups, including the prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT). The incidence of myocardial injury and the number of patients with myocardial injury measured by the indicators of cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) at 48 hours after surgery. Before surgery and at 14 days after surgery, ASIA classification was used to evaluate the neurological functions, including sensory and motor functions between the two groups. The incidence of cardiovascular events at 12 months after surgery were compared between the two groups. Results:A total of 145 patients were followed up for 12-18 months [(15.7±1.6)months]. At 12 months after operation, there were 7 patients in the enhanced heat preservation group were lost to follow-up, compared to 8 patients in the conventional heat preserration group. There was no statistically significant difference in body temperature between the two groups before surgery or at 24 hours after surgery ( P>0.05). At 2 hours during surgery, immediately after surgery and at 2 hours after surgery, the body temperature was (36.90±0.12)℃, (37.00±0.06)℃, and (37.16±0.06)℃ in the enhanced heat preservation group, which were significantly higher than those in the conventional heat preservation group [(36.56±0.03)℃, (36.74±0.08)℃, and (36.84±0.08)℃] ( P<0.01). The serum levels of PT, TT and APTT were not significantly different between the two groups before surgery ( P>0.05), while they were (13.1±1.2)seconds, (19.2±1.1)seconds, and (36.2±3.3)seconds in the enhanced heat preservation group at 4 hours after surgery, which were significantly lower than those in the conventional heat preservation group [(14.3±1.0)seconds, (20.2±1.1)seconds, and (38.7±3.4)seconds] ( P<0.01). The incidence of myocardial injury in the enhanced heat preservation group was 5.0% (4/80) at 48 hours after surgery, which was lower than 12.5% (12/80) in the conventional heat preservation group ( P<0.05). With cTnI as the indicator of myocardial injury, there were 2 patients [2.6%(2/76)] with myocardial injury in the enhanced heat preservation group, which was much lower than 8 patients [11.8%(8/68)] in the conventional heat preservation group ( P<0.05). With hs-cTnT as the indicator of myocardial injury, 8 patients [10.5%(8/76)] in the enhanced heat preservation group experienced myocardial injury, similar with 10 patients [14.7%(10/68)] in the conventional heat preservation group ( P>0.05). There were no statistically significant differences in the ASIA scores of the sensory and motor functions between the two groups before surgery and at 14 days after surgery ( P>0.05). The incidence of cardiovascular events at 12 months after surgery in the conventional heat preservation group was 27.8% (20/72), which was significantly higher than 9.6% (7/73) in the enhanced heat preservation group ( P<0.01). Conclusion:For patients with cervical spinal cord injuries, compared with conventional heat preservation strategies, the enhanced heat preservation strategies in the operating room can improve the patients′ core body temperature and coagulation function, and significantly reduce the incidence of myocardial injury and cardiovascular events.

Objective:To analysis the laws and regulations related to human genetic resources, this study analyzed the current management status and trends at home and abroad, explored the related issues of human genetic resources data management, and provided reference for further promoting and standardizing the management of human genetic resources data in my country.Methods:This article analyzed the current management status of human genetic resources data from three levels: relevant policies, management frameworks, data platforms and sample databases through literature review and expert consultation and policy research.Results:Countries paid more and more attention to human genetic resources, and the construction of my country′s human genetic resources management system is constantly advancing and improving. In the data era, the management of human genetic resources was facing new problems and challenges, requiring further strengthening the research and management of relevant data.Conclusions:At present, the management of human genetic resource data in my country needs to be strengthened. On the one hand, it is necessary to promote the implementation and coordinated management of specific systems on human genetic resources data. On the other hand, it is necessary to strengthen the effective protection and sharing of human genetic resource data.

Objective To improve the efficiency of hospital antimicrobial management and ensure rational clinical use of antimicrobial agents with the aid of antimicrobial stewardship(AMS)empowered by digital intelligence tech-nology in hospital.Methods Information systems such as early warning of antimicrobial indexes,closed-loop ma-nagement of microbial detection information,and decision-making system of antimicrobial resistance monitoring data were applied to the traditional AMS system.Through hospital information systems(HIS)to collect data about thera-peutic antimicrobial use and healthcare-associated infection(HAI)quality control indexes of hospitalized patients in a tertiary first-class public hospital in Shenzhen City before and after digital technology improvement,indexes of 2021 and 2022 were as control group(before improvement)and observation group(after improvement)respective-ly,improvement trend of antimicrobial management was compared.Results After upgrading and renovating the hospital information system,hospital antimicrobial management indexes improved significantly compared to before the renovation.The use rate of antimicrobial agents and the preventive use rate of antimicrobial agents in class Ⅰincision surgery in patients in the observation group were both lower than those in the control group(27.0％vs 38.8％,20.9％vs 23.8％,respectively,both P＜0.05).Antimicrobial use density in hospitalized patients in the observa-tion group was lower than that in the control group([33.27±3.03]DDDs vs[42.06±4.42]DDDs),difference was statistically significant(t=13.11,P＜0.001).The observation group had a higher qualified rate for evaluating antimicrobial medical orders compared to the control group(98.5％vs 96.8％).The pathogenic detection rate of hospitalized patients before therapeutic antimicrobial use and pathogen detection rate related to HAI diagnosis were both higher than those in the control group(87.1％vs 84.5％,99.0％vs 95.4％,respectively),differences were both statistically significant(both P＜0.05).Conclusion Empowering the hospital's AMS system with digital technology can promote more scientific,standardized,efficient,and rational antimicrobial management in hospitals.

Objective To investigate the clinical effect of apical microsurgery combined with guided bone regeneration(GBR)on refractory apical periodontitis and masticatory function.Methods A total of 82 patients with refractory apical periodontitis admitted to our hospital from June 2019 to September 2021 were selected as the study subjects,and they were divided into the control group and the com-bined group according to the random number table,with 41 cases in each group.The control group was treated with apical microsurgery,and the combined group was treated with apical microsurgery combined with GBR.The clinical efficacy,masticatory function and the levels of bone absorption markers[Wnt3a,osteoprotegerin(OPG),receptor activator of nuclear factor-κB ligand(RANKL)]of patients in the two groups were compared.Results The total effective rate of the combined group(100%)was higher than that of the control group(85.37%),the difference was statistically significant(P<0.05).The masticatory efficiency and bite force of patients in both groups increased gradually 3,6 and 12 months after operation(P<0.05),which were higher in the combined group compared with the control group(P<0.05).The tooth mobility of patients in both groups decreased gradually 3,6 and 12 months after operation,and the tooth mobility of patients 3 and 6 months after operation in the combined group were lower than those in the control group(P<0.05).The levels of Wnt3a and OPG of patients 1 week after operation in both groups increased,which were higher in the combined group compared with the control group(P<0.05).The RANKL level of gingival crevicular fluid of patients 1 week after operation in both groups decreased,and which was lower in the combined group compared with the control group(P<0.05).Conclusion The microapical surgery combined with GBR is effective for refractory apical periodontitis,which can effectively inhibit bone resorption,and improve masticatory function.

Objective To investigate the effect of grape seed proanthocyanidins(GSPs)on nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant system and mitochondrial biosynthesis in testes of arsenic-exposed mice.Methods ICR mice were randomly divided into four groups:Control group,model group,GSPs group and experimental group.The mice in the model group and the experimental group drank sodium arsenite solution(10 mg·L-1 arsenic)to induce testicular injury.GSPs group and experimental group were given 100 mg·kg-1 GSPs by gavage,control group and model group were given equal volume of distilled water by gavage once a day for 8 weeks.The histological parameters of testes were measured by hematoxylin-eosin(HE)staining.The contents of malondialdehyde(MDA),superoxide dismutase(SOD)and adenosine triphosphate(ATP)in testicular tissue were determined by kit method.The expression levels of heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQ01)were detected by real-time quantitative reverse transcription polymerase chain reaction(RT-PCR).The expression of Nrf2 protein in testicular tissue was detected by immunohistochemistry.The expressions of mitochondrial synthesis-related proteins were detected by Western blot.Results The diameters of seminiferous tubules in control group,model group,GSPs group and experimental group were(184.32±14.14),(170.41±10.70),(186.87±8.03)and(181.70±9.15)μm;the contents of MDA were(2.30±0.26),(3.28±0.64),(2.32±0.40)and(2.74±0.31)nmol·mg-1;the proportions of Nrf2 positive cells were(46.50±11.98)％,(22.33±8.82)％,(51.67±12.44)％and(39.83±8.35)％;the mRNA expression levels of HO-1 were 1.00±0.21,0.51±0.10,1.00±0.28 and 0.80±0.06;the mRNA expression levels of NQO1 were 1.00±0.18,0.59±0.11,1.09±0.28 and 0.81±0.08;the contents of ATP were(491.83±67.16),(368.81±69.93),(512.44±70.96)and(472.20±68.24)μmol·g-1;the relative expression levels of PGC-1α protein were 1.00±0.06,0.22±0.03,0.94±0.05 and 0.48±0.05;the relative expression levels of TFAM were 1.00±0.07,0.32±0.05,0.80±0.05 and 0.67±0.06.The above indexes in the experimental group were statistically significant compared with the model group(all P＜0.05,P＜0.01).Conclusion GSPs has a protective effect against arsenic-induced testicular injury in mice by activating the Nfr2 antioxidant system and promoting mitochondrial biosynthesis.

Objective To develop a two-dimensional liquid chromatographic method for rifapentine blood concentration determination.Methods The blood concentration of rifapentine was determined by a novel two-dimensional liquid chromatography(2D-LC)with a one-dimensional column:Aston SC2T(3.5 mm ×50.0 mm,5 μm);a two-dimensional column:Aston SCB(4.6 mm ×250.0 mm,5 μm);the temperature of the column was 40 ℃;the flow rate was 1.0 mL·min-1;the detection wavelength was 335 nm;the injection volume was 300 μL.The specificity,standard curve and lower limit of quantification,precision and recovery,and stability of the method were investigated.The method was used to determine the blood concentration of rifapentine in tuberculosis patients.Results Rifapentine showed good linearity within 0.33-18.62 μg·mL-1 with the standard curve equation of y=2.68 x 105x-5 850.36(r=0.997),the recoveries were 99.81％-105.08％,and the intra-and inter-day precision were ≤4.84％.The results of rifapentine blood concentration measurements in tuberculosis patients were in the range of 0.10-54.70μg·mL-1,and 64.74％were within the therapeutic window concentration range(8-30 μg·mL-1).Conclusion The method is easy to operate,has high sensitivity,low detection limit and high specificity,and is suitable for clinical blood concentration determination.Individual differences in the administration of rifapentine in tuberculosis patients are large,and blood concentration monitoring is required for individualized treatment.

Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.