Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

Heart and spleen deficiency syndrome is the most common syndrome type in patients with insomnia. Based on the theory of disease syndrome-combined animal model， this paper used multiple databases to search for the keywords "heart and spleen deficiency"， "insomnia"， "sleepless"， "disease syndrome-combined animal model"， "model evaluation"， etc. It selected the literature related to the animal model of insomnia with heart and spleen deficiency in the past 20 years to evaluate from the aspects of model establishment， modeling factors， syndrome model， disease model， macro characterization & macro characterization evaluation scale， micro indicators， etc. It is found that the existing animal model of insomnia with heart and spleen deficiency is not completely constructed by the method of disease syndrome combination of disease modeling factors and syndrome modeling factors. In the model using this method， the single establishment factor of heart and spleen deficiency does not conform to the clinical reality of disease， and the selection of the factors for the insomnia model is not closely related to or even separated from the syndrome performance. There is a problem of insufficient quantification of macro representation when the macro representation of the model replaces the symptoms related to heart and spleen deficiency syndrome and insomnia in an equivalent manner for macro representation evaluation， which can be improved according to the quantitative ideas and examples of the existing macro representation and macro representation evaluation scale. There are few specific indicators of heart and spleen deficiency syndrome in micro indicators. The micro research of heart and spleen deficiency syndrome and the essence of other traditional Chinese medicine （TCM） syndromes can be carried out by metabonomics and other technologies combined with the theory of corresponding prescription and syndrome， along the specific related ideas of "prescription and syndrome， treatment principle and selection of prescription， treatment principle and selection of acupoints， as well as therapeutic mechanism and syndrome essence". The future users and researchers of animal models of insomnia with heart and spleen deficiency can get improved methods and ideas through the shortcomings of animal models of heart and spleen deficiency listed in this paper and construct animal models of insomnia with heart and spleen deficiency that are more suitable for clinical practice， so as to establish a more perfect modeling method and evaluation system of disease syndrome-combined animal model.

In the context of medical insurance payment reform,the sample hospital has implemented performance management optimization to effectively address the challenges posed by diagnosis-intervention packet(DIP)payment.Reform measures focused on disease quality,rational diagnosis and treatment,operational management,medical technological value,and policy orientation,and they have significantly optimized service ability and performance evaluation indexes of the hospital.Main achievements included a reduction in the cost consumption index and an increase in the clinical performance index,with the overall DIP payment rate increasing from 88.86%to 103.23%and a marked improvement in operational management.The quality control and operational efficiency of the hospital have been effectively enhanced by choosing proper DIP payment evaluation indexes and improving performance management,and provided strong support for the high-quality development of the hospital.

Naval hospitals,the backbone of naval health service system,are the key to build a world-class naval health service system.On the basis of the requirements of military transformation and high-quality development of public hospitals,this paper summarized five aspects of high-quality development of naval hospitals,including directions and regulations,support and contribution of combats,efficiency,sustainable development momentum,and the expansion of service functions.It is very important to strengthen the top-level design and policy support for naval hospitals,to improve the level of governance and innovation,and to find the right target for the naval hospital construction in naval health service system reform.

ObjectiveTo explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.MethodWe used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin (55 mg/kg), geniposide (5 mg/kg), or their 11:1 combination. Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining, Evans blue assay, enzyme-linked immunosorbent assay, and Western blot.ResultsThe results revealed that the nuclear factor-kappa B (NF-κB) signaling pathway is inhibited in combination treatment of cerebral ischemia. Ten targets were identified as key nodes in the protein–protein interaction network: interleukin 6 (IL-6), interleukin-1β, interleukin 18, C–C motif ligand 2, C–C motif ligand 4, interleukin 10, interferon-γ-inducible protein 10, C–C motif ligand 3, tumor necrosis factor-α (TNF-α), interleukin-1α. The baicalin-geniposide combination significantly reduced infarct volume, improved neurological deficits, and alleviated brain edema/blood–brain barrier leakage compared with monotherapy. Additionally, it significantly inhibited toll-like receptor 4 (TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-α and IL-6 levels.ConclusionThe baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.

Objective:To explore the value of applying multiple genetic testing techniques for the prenatal diagnosis of Turner syndrome fetuses with complex mosaic small supernumerary marker chromosomes (sSMC).Methods:Chromosomal karyotypes of amniotic fluid samples from 5 030 pregnant women who had undergone amniocentesis at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University from January to December 2022 were retrospectively reviewed. Three fetuses with complex mosaicism fetuses (carrying 2 types of sSMC) were selected as the study subjects. Genetic tests including G-banded chromosomal karyotyping analysis, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) were used to clarify the origin and mosaic status of the sSMC. This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (No. 2023-159-01).Results:G-banded chromosomal analysis of fetus 1 showed a karyotype of 45, X[64]/46, X, + mar1[13]/46, X, + mar2[3]. FISH results showed that 52% of of its cells had contained one X chromosome signal, whilst 48% contained two X chromosome signals. CMA results revealed the fetus had harbored a 32.32 Mb and a 50.93 Mb deletion in Xp22.33p21.1 and Xq22.2q28 regions, respectively, in addition with mosaic deletions of approximately 1.43 copies, 1.78 copies and 1.43 copies in the Xp21.1p11.1, Xq11.1q21.1 and Xq21.2q22.2 regions, respectively. The fetus 2 had a karyotype of 45, X[27]/46, X, + mar1[14]/46, X, + mar2[12]. FISH results indicated that 88% of its cells contained one X chromosomes signal and two Y chromosome signals, and 12% contained signals for one X chromosomes signal and one Y chromosome signal. CNV-seq results revealed a deletion of 7.74 Mb in the Yq11.222q11.23 region and a mosaic duplication of approximately 1.738 copies in the Yp11.31q11.221 region. The fetus 3 had a karyotype of 45, X[60]/46, X, + mar1[11]/46, X, + mar2[6]. FISH results showed that 28% of its cells contained one X chromosome signal, and 72% contained tow X chromosome signals. CNV-seq results revealed deletions of 55.60 Mb and 53.50 Mb in the Xp22.33p11.1 and Xq22.1q28 regions, respectively, along with a mosaic deletion of approximately 1.85 copies in the Xp11.1q13.2 region and a mosaic repeats of approximately 2.66 copies in the Xq13.2q22.1 region. The sSMCs in the 3 fetuses had all originated from sex chromosomes and were of complex mosaic type. After genetic counseling, the three couples had all opted to terminate the pregnancy.Conclusion:The combined use of multiple genetic testing techniques has determined the origin and structure of complex mosaic sSMCs and provided a basis for prenantal diagnosis and genetic counseling.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

UNC-51-like kinase 1(ULK1)is an important factor involved in regulating the initiation of autophagy.ULK1 regu-lates inflammatory cytokines through autophagy and mitochondrial oxidative stress,and is involved in the pathological processes of var-ious diseases.ULK1 and its complexes are regulated by rapamycin(mTOR)and AMP-activated protein kinase(AMPK)to initiate au-tophagy,thereby exerting differential effects on a variety of inflammatory diseases.In inflammatory diseases,mitochondrial oxidative stress can induce ULK1 into the nucleus to accelerate apoptosis.Therefore,ULK1 plays different important roles in inflammatory dis-eases.For example,ULK1 initiates airway epithelial mitochondrial autophagy in asthma,participates in mitochondrial oxidative stress in acute liver failure,affects related inflammatory factors in atherosclerosis,and modulates beneficial effects of autophagy in diabetes.This article reviews the biological function of ULK1,its impact on inflammatory diseases and the research progress of targeted drugs.

Objective To explore the medication law of Professor Wang Qingguo for the treatment of insomnia based on data mining technology.Methods Paper-based prescriptions for Professor Wang Qingguo's treatment of insomnia from December 2016 to August 2023 were collected and a database was constructed.The screened prescriptions were subjected to data mining such as frequency statistics,association rule analysis,and clustering analysis.Results Totally 399 effective outpatient prescriptions were screened-out,involving 276 kinds of Chinese materia medica,with a total frequency of 6738 times.There were 38 Chinese materia medica with a frequency of use≥50.The properties were mainly warm,cold and mild,the tastes were mainly sweet,bitter and pungent,and mainly belong to the lung,spleen and heart meridians.Association rule analysis showed that the most commonly used drug combinations were"Fructus Tritici Levis-Scutellariae Radix-Bupleuri Radix","Pericarpium Citri Reticulatae-Scutellariae Radix-Pinelliae Rhizoma",etc.Association rule network analysis obtained a core prescription containing 12 kinds of Chinese materia medica for insomnia.Four new drug combinations were obtained by clustering analysis.Conclusion Professor Wang's treatment of insomnia has the characteristics of following the original meaning of Huang Di Nei Jing and Nan Jing,making good use of the classical prescription,applying combined prescription,flexible use of prescription,combining ancient and modern prescriptions,using specific medicine.It deeply reflects the academic view of"Tongping Zhihe".

Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.