FU Qingzhu Nyuke·Zhongzi is a concentrated manifestation of Fu′s academic thoughts of promoting conception (Zhongzi), which affects the treatment of infertility in later generations. However, the Zhongzi chapter is named after "symptoms" and is not divided into chapters according to "syndromes, "limiting the clinical application of Fu′s thoughts of Zhongzi. The "qi circle in round" theory is the crystallization of HUANG Yuanyu′s academic thinking, advocating for qi transformation, emphasizing middle qi, and considering the four phenomena. This theory highlights the role of middle qi in the rise, fall, and circulation of disease development. The "qi cycle in round" theory, a comprehensive view of Fu′s Zhongzi chapter, reveals that FU Qingzhu emphasizes the transformation of visceral qi in diagnosing and treating infertility, focusing on the spleen, liver, and kidneys. His prescription aims to restore the overall qi mechanism of the body, highlighting the circulation of middle earth and the dredging of meridians, aligning perfectly with the theory of the "qi cycle in round." Therefore, this article argues from the perspective of the "qi cycle in round, "deconstructing the pathogenesis of Fu′s infertility based on the dereliction of spleen earth, stagnation of liver wood, and kidney yin and yang deficiency. It reorganizes Fu′s formula system of Zhongzi by mediating middle earth, soothing liver depression, and regulating kidney function, summarizing the characteristics of Fu′s thoughts of Zhongzi with the aid of qi around the waist and navel, simultaneous treatment of conqenital and acquired essence, and restriction and generation of five phases. Based on the "qi cycle in round" theory, this study explores Fu′s academic thoughts of Zhongzi to strengthen the organic integration of Fu′s academic thoughts of Zhongzi with the theory of "qi cycle in round, "providing new perspectives for the study and inheritance of Fu′s academic thoughts of Zhongzi.

ObjectiveTo explore the mechanism of action of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma in the treatment of recurrent spontaneous abortion （RSA） through network pharmacology， molecular docking， and cell experiment verification. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and UniPort databases were used to screen and organize the active ingredients and corresponding targets of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma. The potential therapeutic targets of RSA were screened in Online Mendelian Inheritance in Man （OMIM）， GeneCards database， DrugBank database， DisGeNET database， and Therapeutic Target Database （TTD）. The potential core targets of Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma for treating RSA were further screened by constructing a protein-protein interaction （PPI） network and topological analysis. Meanwhile， the Database for Annotation， Visualization and Integrated Discovery （DAVID） was chosen to perform enrichment analysis on intersection targets. On this basis， AutoDock software was used for molecular docking， and the data were imported into PyMOL software for visualization and composition. Finally， the cell counting kit-8 （CCK-8） experiment， Transwell cell invasion assay， and Western blot were used to detect the effects of serum containing Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma on HTR-8/SVneo cells and observe the effects on the interleukin （IL）-6/signal transducer and activator of transcription 3（STAT3） signaling pathway and related proteins. ResultsThrough network pharmacology analysis， a total of 69 active ingredients， 73 potential therapeutic targets， and 17 core targets， including IL-6， IL-10， and STAT3， were collected. The 73 common targets were enriched in 614 Gene Ontology （GO） entries and 57 Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways. The molecular docking results indicated that IL-6 and STAT3 had good binding ability with the main active ingredients， including matrine， cryptotanshinone， and tanshinone Ⅱ_A. The cell experiment results showed that， compared with those of the control group， after 24 hours of treatment with the drug-containing serum， the survival and invasion rates of HTR-8/SVneo cells were significantly increased （P<0.05）， and the expression of IL-6/STAT3 signaling pathway and related proteins IL-10 and c-Myc was significantly elevated （P<0.05）. Moreover， the trend of action in the drug-containing serum group was consistent with that of pathway agonists. ConclusionCuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma may enhance the survival rate and invasive activity of HTR-8/SVneo cells to further prevent and treat RSA by activating the IL-6/STAT3 signaling pathway and upregulating the expression of downstream factors IL-10 and c-Myc in the pathway.

Objective To track and evaluate the implementation and application of the occupational health standard Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of ²⁵²Cf neutron afterloading (GBZ/T 201.4-2015) by radiation health technical service agencies, medical institutions, health supervision agencies, and radiotherapy facility design units, and to provide a scientific basis for the further revision and implementation of this standard. Methods Following the Guideline for health standards tracking evaluation (WS/T 536-2017) and the project implementation plan, relevant practitioners were randomly selected for a questionnaire survey. The survey primarily focused on their awareness, standard training, application, and revision suggestions of GBZ/T 201.4-2015. The results were summarized and analyzed. Results A total of 168 evaluation questionnaires were collected from relevant practitioners in 28 provinces. Only 31.6% of the respondents reported being “well familiar” or “ familiar” with the standard, 27.4% of the respondents believed that the standard was widely used, and 45.2% of the respondents believed that the standard could meet the needs of their work. Only 14.9% of the respondents had received relevant training on the standard, more than half of the respondents had not applied the standard within the past 10 years, and 45.2% of the respondents believed that the standard "needs to be revised". Conclusion Due to the small number of californium-252 neutron afterloading radiotherapy devices in operation on the market, the overall awareness of the standard is low, suggesting that relevant authorities need to strengthen training and publicity of the standard, and that certain sections of the standard need to be revised or merged.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Background::The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.Methods::The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.Results::The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, ?1.0 to ?0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019. Conclusions::Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

AIM:To clarify the effect of macrophage PKM2 deficiency on mucosal repair in ulcerative colitis(UC).METHODS:The gene expression and metabolic profiles in UC patients were first analyzed based on the following databases:PXD001608,GSE193677,and GSE214695.Using the macrophage-specific PKM2 elimination mice(PKM2ΔMAC),the functions of PKM2 in dextran sulfate sodium(DSS)-induced UC were clarified in vivo by analyzing the body weight,disease activity index(DAI)scores,HE staining,immunohistochemical staining,and expression of muco-sal barrier markers.The impact of PKM2 on macrophage polarization was also investigated by flow cytometry,RNA se-quencing and RT-qPCR in mouse bone marrow-derived macrophages(BMDMs)and THP-1 cells in vitro.RESULTS:Bioinformatic analysis suggested that the intestinal tissues of UC patients preferred glycolysis.The expression of PKM was parallel to the severity of UC in patients,and the expression of PKM2,but not PKM1,was elevated in macrophages of UC mice.In the DSS-induced UC mice,macrophage-specific PKM2 elimination significantly alleviates the body weight loss,diarrhea,rectal bleeding,colonic shorten,as well as decreased DAI scores and mucosal tissue damage.The BMDMs de-rived from the PKM2ΔMAC mice preferred the M2 polarization upon LPS or IL-4 stimulation to that derived from the wild-type mice,as indicated by the F4/80+CD45+CD86+and F4/80+CD45+CD206+population,as well as the expression of Ocln,F11r and Tjp-1.The RNA sequencing results indicated significant gene differential expression in PKM2 knockout mouse macrophages,which was enriched in biological processes such as leukocyte migration,tissue remodeling,and cytokine in-teractions.Macrophage PKM2 deficiency promoted the expression of mucosal repair factors(Il8,Cxcl1,Ptgs2 and Wnt6),which was further validated in PKM2 knockout THP-1 cells.CONCLUSION:The PKM2 deficiency in macro-phages benifits the mucosal repair in UC status via facilitating the wound-healing macrophage polarization.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

OBJECTIVE： To establish the method for simultaneous determination of four known related substances （olmesartan，olmesartan ester dimer ，olmesartan ester alkene ，benzothiadiazine impurity ，called impurity A ，B，C，D for short ）in Olmesartan medoxomil hydrochlorothiazide tablets. METHODS ：HPLC-principal component self-control with correction factor were adopted. The determination was performed on YMC-Triart C 8 column with mobile phase A consisted of acetonitrile- 0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（70 ∶ 30，V/V），mobile phase B consisted of acetonitrile-0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（15 ∶ 85，V/V）at the flow rate of 0.8 mL/min（gradient elution ）. The detection wavelength was set at 265 nm，and column temperature was 25 ℃. The temperature of injector was 4 ℃；the injection volume was 10 μL. RESULTS：The correction factors of impurity A ，B，C，D were 1.42，1.17，0.89，0.92，respectively. The linear range of olmesartan medoxomil ，hydrochlorothiazide and impurity A ，B，C，D were 0.252 7-7.580 0，1.152 1-4.562 9，0.244 0-18.299 0，0.244 7-3.670 8，0.265 2-3.978 3 and 0.149 9-4.497 3 μg/mL（r≥ 0.999 7），respectively. The limits of detection were 0.084 2，0.050 7，0.081 3，0.081 6，0.088 4，0.050 0 μg/mL，respectively. The quantitative limits were 0.252 7，0.152 1，0.244 0，0.244 7，0.265 2 and 0.149 9 μg/mL，respectively. The results of intermediate precision ，stability（24 h）and repeatability tests all met the relevant requirements. The average recovery rates were 104.00％-108.04％，102.00％-104.94％，100.99％-106.89％，92.00％-95.18％，102.00％-105.06％，103.90％-107.00％（n＝3）， respectively. The contents of impurity A ，B and D in 3 batches of Olmesartan medoxomil hydrochlorothiazide tablets were 0.90％ -1.00％ ，0-0.11％ ，0.16％ -0.24％ ，respectively. The impurity C and other impurities were not detected. There is no significant difference between the results measured by the established method and by the external standard method. CONCLUSIONS：The method has been proved to be highly sensitive and reproducible. It can be used to simultaneously determine four known substances in Olmesartan medoxomil hydrochlorothiazide tablets.

Carbon nanomaterials are one of the hotspots in the research of drug delivery systems for cancer. Compared with the traditional drug delivery systems for cancer treatment, carbon nanomaterials can be used as drug carriers after modification based on their advantages of large specific surface area and unique optical properties. They have the characteristics of high drug loading, good biocompatibility, tumor targeting and lasting action time, indicating great potential and development space. In this paper, the properties and functions of quantum dots, carbon nanotubes, graphene oxide and mesoporous carbon nanospheres are introduced in the order of dimensional quantum properties. The current research focus and existing problems of carbon nanomaterials are discussed in order to provide a reference for the safe and effective application of carbon nanomaterials in tumor therapy.