ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction （HBY） repairs the intestinal mucosal injury in the rat model of ulcerative colitis （UC） via the miR-21/suppressor of cytokine signaling 1 （SOCS1）/Janus kinase 1 （JAK1）/signal transducer and activator of transcription 6 （STAT6） signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups： blank， model， low-dose （3.68 g·kg^-1） HBY， medium-dose （7.35 g·kg^-1） HBY， high-dose （14.5 g·kg^-1） HBY， and mesalazine （0.035 g·kg^-1）， with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining， and the Robarts histopathology index （RHI） was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines ［interleukin （IL）-6， IL-18， IL-1β， and tumor necrosis factor-α （TNF-α）］ in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21， SOCS1， JAK1， and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1， JAK1， phosphorylated （p）-JAK1， STAT6， p-STAT6， Occludin， and Claudin-1 in the colon tissue. ResultsCompared with the blank group， the model group showed an increase in disease activity index （DAI） （P<0.01）， shortening of colon length （P<0.01）， severe histopathological damage in the colon tissue， and an increase in RHI， rises in serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， up-regulation in mRNA levels of miR-21， JAK1， and STAT6 and protein levels of p-JAK1 and p-STAT6 （P<0.01）， and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 （P<0.01）. The treatment with HBY reduced the DAI （P<0.01）， alleviated colon shortening and histopathological damage in the colon tissue， decreased the RHI （P<0.01）， lowered the serum levels of IL-6， IL-1β， IL-18， and TNF-α （P<0.01）， down-regulated the mRNA levels of miR-21， JAK1， and STAT6 （P<0.05， P<0.01）， up-regulated the mRNA level of SOCS1 （P<0.05）， up-regulated the protein levels of SOCS1， Occludin， and Claudin-1 （P<0.05， P<0.01）， and down-regulated the protein levels of p-JAK1 and p-STAT6 （P<0.05， P<0.01）. ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.

Since 1986, the WHO has held ten global health promotion conferences covering various health promotion issues and sustainable development worldwide. These sessions have formed a series of consensus and actions that guide promoting health globally. This study analyzed the declarations, reports, and news materials from the ten conferences that studied health promotion action areas, focal topics, actor networks, partnership relationships, and other significant outcomes. It also explored how these conferences contributed to the construction and advancement of global health promotion consensus and actions. The first Global Conference on Health Promotion identified the concept of health promotion and five key action areas, laying the foundation for subsequent conferences and health promotion actions. Over the years, the ten conferences continuously expanded the essence of health promotion, developed partnership relationships, formulated public health promotion policies, and called for health promotion actions. This process culminated in the formation of global consensus and collective actions. The latter conferences have gained significant attention and influence. The conferences offer valuable insights for future global health promotion endeavors and provide global perspectives and pathways for the development of Healthy China.

Background and purpose:Exogenous bone morphogenetic protein 9(BMP9)inhibits the malignant progression of human breast cancer,but its expression is often abnormally low in breast cancer.In this study,we intended to explore the expression and role of epigenetically-modified histone lysine-specific demethylase 4A(KDM4A)in breast cancer,and to investigate the relationship between KDM4A and BMP9 and its possible regulatory mechanism.Methods:The expression of KDM4A in breast cancer and its relationship with BMP9 were analyzed by bioinformatics and verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Chromatin immunoprecipitation(ChIP)verified the regulatory role of KDM4A on BMP9,and RNA stability experiments and CHX protein stability experiments verified the effect of KDM4A in BMP9 expression.Exogenous recombinant MDA-MB-231 cells transfected with KDM4A small interfering RNA(siKDM4A)or infected with siBMP9 adenovirus(Ad-siBMP9)were constructed using RNA interference technology and adenoviruses knocking down BMP9,and the migratory and invasive abilities of the cells were detected by scratch healing assay and transwell assay,respectively.Results:Bioinformatics analysis showed that the expression of KDM4A was significantly higher in breast cancer than in normal tissues,and there was a negative correlation between the expression of KDM4A and that of BMP9 in breast cancer;RTFQ-PCR and Western blot showed that KDM4A was highly expressed in different breast cancer cell lines,and the knockdown of KDM4A significantly up-regulated BMP9.ChIP experiment confirmed that KDM4A could be significantly enriched in the promoter region of BMP9 gene,reducing its histone lysine 36 position instead of position 4 methyl status,thus silencing the expression of BMP9.RNA stability assay and CHX protein stability assay confirmed that KDM4A had no significant effect on the mRNA of BMP9,but could affect its protein degradation.After knocking down KDM4A,the migration and invasion abilities of breast cancer cells MDA-MB-231 were significantly inhibited,and this effect could be partially reversed by knocking down BMP9.Conclusion:KDM4A is highly expressed in breast cancer and breast cancer cell MDA-MB-231,and can silence its expression by down-regulating the level of histone methylation in the promoter region of the BMP9 gene,as well as affecting the stability of BMP9 at the protein level rather than at the level of mRNA,and promoting the migration and invasion of breast cancer.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Objective To investigate the influence of individualized low-dose CT imaging parameters on quantitative computed tomography(QCT)liver fat content measurement and image quality by using the combined technique of Auto-prescription and adaptive statistical iterative reconstruction(ASIR-V)algorithm with different weights.Methods A total of 231 patients who underwent both chest and abdominal CT scans were prospectively selected.The overlapping liver of two-position scans in the same case was studied,in which the chest was scanned with an individualized low-dose protocol(group A)and the upper abdomen was scanned with a routine 120 kVp protocol(group B).Patients with group A were scanned by using 80 kVp and 100 kVp based on Auto-prescription technique,and divided into the subgroups of A1 and A2;meanwhile the same patients with group B were scanned by using 120 kVp and divided into the subgroups of B1 and B2.The images were transferred to AW4.6 and QCTpro workstations for measuring CT values,standard deviation(SD)values and Fat％QCT values of the left lobe,right anterior lobe,and right posterior lobe of the liver in the overlapping regions.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were also calculated using the same-level erector spinae as background.Paired sample t-test was employed to compare the differences in Fat％QCT measurements between groups A and B.Spearman correlation analysis was conducted,and linear regression equations were established.Two observers evaluated image quality using a five-point scale and Kappa test was conducted to test inter-observer consistency.Results In group A,the Fat％QCT values showed no statistically significant difference among different weights of ASIR-V.However,the statistically significant difference was found between groups A and B(P＜0.05),and there were highly positive correlations between subgroups A1 and B1 and between subgroups A2 and B2(r=0.939 7,0.987 2,P＜0.05).The linear regression equation under 80 kVp and 100 kVp were as follows:y=0.976x+3.119,y=1.007x+2.041.The SNR and CNR of group A combined with post-60％ASIR-V were higher than those of group B combined with post-40％ASIR-V under conventional tube voltage.The subjective scores between groups A and B had no statistically significant difference.Conclusion Low-dose chest imaging based on Auto-prescription technique combined with post-60％ASIR-V can not only satisfy clinical diagnostic requirement,but also realize quantitative analysis of Fat％QCT under low tube voltage(80 kVp/100 kVp).

Objective:To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI) and summarize the single-center experience.Methods:A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide, admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022. The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results:The study included 5 patients, 3 males and 2 females. The age of onset ranged from 1 to 90 days. Initial symptoms included poor mental state(2/5) and convulsions(3/5). Blood glucose levels were 1.1 to 2.3 mmol/L, and insulin levels ranged from 13.52 to 70.53 μIU/mL. Two cases were classified as diffuse type, and the histological type of 3 cases was unknown. Genetic testing confirmed the diagnosis, with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del). Of the five patients, three patients were treated with sirolimus after diazoxide and octreotide failed, one patient was treated after unresponsive diazoxide, and the other one was treated after diazoxide, octreotide, and even near-total pancreatectomy failed. The onset age of sirolimus therapy ranged from 1 to 20 months. The maximum dosage of sirolimus was 1.2-3.2 mg·m -2·d -1, and the duration of medication ranged from 2 to 12 months. One patient was fully responsive to sirolimus, and the other four patients were partially responsive. All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment. During follow-up, non-infectious diarrhea, elevated carcinoembryonic antigen, elevated triglycerides, and elevated liver enzymes were observed. Conclusion:This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective. However, the long-term efficacy and safety warrant further multicenter trials.

Humans ; Pharmacogenetics ; Precision Medicine ; Glaucoma/genetics*

Objective:To optimize the clinical nursing pathway, service program and evaluation parameters of percutaneous coronary intervention(PCI), for references for the cost accounting and compensation mechanism of nursing program in public hospitals.Methods:After literature analysis and group discussion, the initial templates were constructed for the PCI clinical nursing pathway, nursing service projects, and their evaluation parameters. 15 experts were consulted by two rounds of Delphi method to optimize PCI nursing path, nursing service items and their evaluation parameters (basic labor consumption, basic time consumption, technical difficulty and risk degree).Results:Two rounds of Delphi method finally determined the PCI clinical nursing path and 27 nursing service items, and adjusted the evaluation parameters of 10 nursing service items. The new projects for PCI clinical nursing services included adjustment and review of dual antiplatelet therapy plans, postoperative rehabilitation nursing, and key project verification. The three nursing service projects with the highest level of technical difficulty and risk were intravenous blood transfusion, gastric catheterization, and gastrointestinal decompression. The two items with the highest importance assigned were high pump assisted arterial/venous infusion (blood) and invasive continuous arterial blood pressure monitoring.Conclusions:The PCI clinical nursing pathway and nursing service project constructed in this study could closely integrate with clinical practice, highlight the integrated nursing service model, and reflect the labor value of nurses.

Objective To investigate the expression and significance of CD19+CD24hiCD38hi regulatory B lymphocytes and secreted cytokine interleukin-10(IL-10)in hypertensive disorder complicating pregnancy.Methods A total of 15 patients with gestational hypertension(the gestational hypertension group)and 11 pa-tients with preeclampsia(the preeclampsia group)admitted to this hospital from September 2020 to May 2021 were selected,and 12 normal pregnant women(the control group)were selected during the same period.Flow cytometry was used to detect the expression of CD19+B lymphocytes,CD19+CD24hiCD38hi regulatory B lym-phocytes,and IL-10 in peripheral blood of three groups of pregnant women before termination of pregnancy.Results There was no statistically significant difference in the percentage of serum CD19+B lymphocytes a-mong the three groups(P＞0.05).The results of pairwise comparison showed that the percentage of serum CD19+CD24hiCD38hi regulatory B lymphocytes in the control group was higher than that in the gestational hy-pertension group,and it was higher than that in the preeclampsia group.And the differences between the con-trol group and the gestational hypertension group and the preeclampsia group were statistically significant(P＜0.05).The results of pairwise comparison showed that the serum level of IL-10 in the control group was higher than that in the gestational hypertension group,and it was higher than that in the preeclampsia group.And the difference between any two groups was statistically significant(P＜0.05).Conclusion CD19+CD24hiCD38hi regulatory B lymphocytes and secreted IL-10 are abnormally expressed in women with hypertensive disorder complica-ting pregnancy,which may be related to the occurrence and development of gestational hypertension.

In recent years, there has been increasing evidence that nonalcoholic fatty liver disease (NAFLD) is a manifestation of a systemic metabolic disease in liver. However, limitations in the definition and diagnostic criteria of NAFLD could not fully and accurately describe the metabolic disorder. A consensus statement proposed renaming NAFLD to metabolic associated fatty liver disease (MAFLD). Compared with NAFLD, MAFLD links fatty liver disease with metabolic factors such as overweight or obesity and diabetes, and the diagnosis of the disease no longer excludes the presence of metabolic abnormalities in patients with alcohol consumption or other chronic liver diseases. The authors focus on definition changes of fatty liver disease, discuss the epidemiological changes from NAFLD to MAFLD and the relationship of MAFLD with liver fibrosis and extrahepatic diseases, and also the significance of MAFLD for public health.