Objective:To compare Al 18F-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with 18F-FDG PET/CT in the evaluation of patients with initial gastric cancer. Methods:Twenty patients (13 males, 7 females, age: 27-77 years) with histologically proven gastric cancer were recruited prospectively between March 2021 and July 2022 in the First Affiliated Hospital of Zhengzhou University. Each patient underwent both 18F-FDG and Al 18F-NOTA-FAPI-04 PET/CT within one week. SUV max, tumor background ratio (TBR) and positive detection rate of the two methods were compared (Wilcoxon signed rank sum test, McNemar χ2 test). Results:Al 18F-NOTA-FAPI-04 showed higher SUV max and TBR than those of 18F-FDG in primary tumors (10.2(8.0, 13.7) vs 5.2(3.3, 7.7), z=-3.47, P=0.001; 7.6(5.6, 10.3) vs 2.4(1.8, 3.0), z=-3.85, P<0.001). For the detection of primary gastric cancer, the positive detection rate of Al 18F-NOTA-FAPI-04 PET/CT showed the trend of being higher than that of 18F-FDG PET/CT (95%(19/20) and 75%(15/20); χ2=2.25, P=0.125). For assessing lymph node metastasis, the detection rate of Al 18F-NOTA-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT (78.9%(101/128) vs 64.8%(83/128); χ2=13.47, P<0.001). The SUV max and TBR of Al 18F-NOTA-FAPI-04 in lymph node were higher than those of 18F-FDG (5.3(3.5, 9.2) vs 2.8(1.8, 4.7), z=-7.31, P<0.001; 4.6(2.6, 6.5) vs 1.7(1.0, 3.0), z=-8.44, P<0.001). For the detection of peritoneal carcinomatosis, Al 18F-NOTA-FAPI-04 PET/CT showed higher peritoneal cancer index (PCI), SUV max, and TBR compared to 18F-FDG PET/CT (PCI: 12.0(3.0, 29.8) vs 5.5(0.5, 17.5), z=-2.22, P=0.026; SUV max: 8.2(4.4, 12.5) vs 2.7(1.9, 4.0); z=-2.52, P=0.012; TBR: 5.1(2.9, 13.3) vs 1.1(0.9, 2.0); z=-2.52, P=0.012). Conclusion:Al 18F-NOTA-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in primary and metastatic lesions of gastric cancer and might be a potential novel modality for imaging patients with gastric cancer.

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Objective:To analyze the nationwide epidemiological characteristics and trend of hand, foot and mouth disease (HFMD) fatal cases from 2008 to 2022 and provide evidence for the prevention and control of HFMD.Methods:The information on HFMD fatal cases during 2008 to 2022 was collected from the National Notifiable Disease Surveillance Reporting System of China. Data of the epidemiological characteristics was analyzed by R 4.2.2 software and the changing trends for the case fatality rates, mortality rates and their age-adjusted rates were analyzed by Joinpoint 4.9.10 software.Results:From 2008 to 2022, a total of 3 704 fatal HFMD cases were reported in China. The fatal cases were primarily observed in children aged <3 years (83.42%, 3 090/3 704). The male and female gender ratio was 1.82 ∶1 (2 389 ∶1 315). Regarding the age-adjusted case fatality rates over time, there was a rapid increase from 2008 to 2010 [annual percentage change (APC) =41.97%, P<0.05]. From 2010 to 2016, a steady decline was observed (APC=-28.57%, P<0.05), and the decline accelerated (APC=-39.66%, P<0.05) from 2016 to 2022. Since 2020, less than 10 fatal cases were reported annually nationwide. Among the 2 566 laboratory-confirmed deaths from 2008 to 2022, Enterovirus A71 (EV71) was the predominant pathogen (91.62%,2 351/2 566). There have been noticeable changes in the pathogen composition since 2017, decreasing in EV71 and increasing in the proportion of fatalities caused by Coxsackievirus A16 (CV-A16) and other enteroviruses. Conclusions:From 2008 to 2022, the HFMD case fatality rates and mortality rates continuously declined, peaked in 2010. Since 2017, the decline of HFMD case fatality rates has been noticeably accelerated. Along with the decrease in the proportion of EV71 in HFMD fatal cases, the proportion of other enteroviruses appeared increasing. It is essential to continuously monitor the etiological spectrum of the fatal cases.

Objective To study the effects of ultrasound-guided quadratus lumborum block(QLB)on intraoperative hemodynamics and opioid dosage in emergency patients with ectopic pregnancy.Methods A total of 70 patients with ectopic pregnancy undergoing laparoscopic surgery in Langfang People's Hospital from January 2021 to February 2024 were selected as subjects.According to the different anesthesia methods,the patients were divided into the control group and the study group,with 35 cases in each group.The control group was given general anesthesia,while the study group additionally added ultrasound-guided QLB.The intraoperative sedation effect,hemodynamics,postoperative pain,incidence of adverse reactions and opioid use at different times(admission,entry,intubation,skin incision,extubation,and discharge)were observed in the two groups.Results There were no statistically significant differences in the onset time of sedation,the rate of salvage sedation,the incidence of intraoperative body movements,the modified observer's assessment of alert/sedation(MOAA/S)at each time,and the hemodynamics at the time of admission,entry and intubation between the two groups.The mean arterial pressure(MAP),systolic blood pressure(SBP)and heart rate(HR)in the study group were significantly lower than those in the control group during skin incision,extubation and discharge[skin incision:MAP(mmHg,1 mmHg≈0.133 kPa)was 85.24±4.59 vs.96.95±4.68,SBP(mmHg)was 92.24±4.85 vs.99.49±5.13,HR(times/min)was 85.33±2.96 vs.94.51±2.92;extubation:MAP(mmHg)was 94.84±5.02 vs.102.05±5.13,SBP(mmHg)was 96.48±4.72 vs.105.03±5.07,HR(times/min)was 95.51±4.95 vs.102.49±5.87;discharge:MAP(mmHg)was 86.14±4.99 vs.93.71±5.25,SBP(mmHg)was 96.48±4.69 vs.104.37±5.02,HR(times/min)was 84.05±4.57 vs.90.51±4.86,all P<0.05]and pulse oxygen saturation(SpO2)was higher than those in the control group(skin incision:0.988 5±0.012 2 vs.0.965 4±0.012 3,extubation:0.974 7±0.012 4 vs.0.963 2±0.012 1,discharge:0.981 1±0.012 4 vs.0.970 3±0.012 3,all P<0.05).The resting numeric rating scale(NRS)scores and active NRS scores in the study group were lower than those in the control group at 3,6,12,and 24 hours after surgery,the random time was prolonged,the resting NRS and active NRS in the two groups gradually increased,reaching a peak at 24 hours after surgery,and the resting NRS and active NRS in the study group were significantly lower than those in the control group(resting NRS:3.86±0.82 vs.4.53±1.04,active NRS:4.26±1.05 vs.4.85±1.13,all P<0.05).The incidence of adverse reactions in the study group was lower than that in the control group[11.43%(4/35)vs.34.29%(12/35),P<0.05].The dosage of Sufentanil in 24 hours and 48 hours,the number of analgesic pump in 48 hours and the number of relief analgesia cases in the study group were lower than those in the control group[the dosage of Sufentanil in 24 hours(μg):23.28±4.02 vs.36.14±4.57,the dosage of Sufentanil in 48 hours(μg):41.61±4.82 vs.59.33±6.25,the number of analgesic pump in 48 hours(times):2.94±1.22 vs.6.15±1.71,the proportion of relief analgesia:8.57%(3/35)vs.28.57%(10/35),all P<0.05].Conclusion Ultrasound-guided QLB can reduce hemodynamic fluctuations,relieve postoperative pain,reduce adverse reactions and opioid use in emergency patients with ectopic pregnancy,demonstrating a positive impact.

Objective To observe the effect of quadratus lumborum block(QLB)anesthesia on intraoperative blood gas indexes and postoperative recovery in female uremic patients with peritoneal dialysis catheterization.Methods A total of 70 female uremic patients with peritoneal dialysis catheterization admitted to Langfang People's Hospital from January 2021 to December 2023 were selected as the research objects.According to the random number table method,they were divided into the control group and the study group,with 35 cases in each group.The control group was given conventional local infiltration anesthesia,whereas the study group was given QLB anesthesia.The changes of mean arterial pressure(MAP),heart rate(HR),blood gas indexes[pulse oxygen saturation(SpO2),arterial partial pressure of carbon dioxide(PaCO2)]and numeric rating scale(NRS)score,at different points pain factors[5-hydroxytryptamine(5-HT),substance P(SP),norepinephrine(NE)]before operation and 24 hours after operation,postoperative recovery(time to get out of bed for the first time,exhaust time,length of hospital stay)and adverse reactions were observed in the two groups.Results There was no significant difference in MAP,HR,blood gas index and NRS score between the two groups at the admission.The MAP,HR,PaCO2 in the study group were significantly lower than those in the control group during skin incision,rectus abdominis separation,catheterization,suture,and leaving the room,and SpO2 was significantly higher than that in the control group,and NRS score in the study group were significantly lower than those in the control group during skin incision,rectus abdominis separation,catheterization,suture(all P<0.05).There was no significant difference in the levels of 5-HT,SP and NE between the two groups before operation,but the levels of 5-HT,SP and NE at 24 hours after operation were significantly higher than those before operation,but the levels of 5-HT,SP and NE in the study group were lower than those in the control group.The first ambulation time,exhaust time and hospitalization time in the study group were significantly shorter than those in the control group(all P<0.05).The incidence of nausea and vomiting,constipation,pruritus,dizziness and other adverse reactions in the study group was significantly lower than that in the control group(all P<0.05).Conclusion QLB can reduce the fluctuation of intraoperative blood gas indexes in female uremic patients with peritoneal dialysis catheter,relieve postoperative pain,reduce the level of pain factors and reduce the occurrence of adverse reactions,and has a good effect on promoting postoperative recovery of patients.

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1^LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8⁺ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

Objective:To analyze the implementation of early essential newborn care (EENC) in baby-friendly hospitals in China.Methods:This is an investigation carried out using convenience sampling method. People in charge of labor ward, obstetric wards or neonatology department of the selected hospitals, such as baby-friendly hospitals with birth facilities, primary or higher level of hospitals, or general hospitals or those specialized in obstetrics and gynecology or materal and child health care centers, were selected as the subjects of the survey. Information about EENC practices in these hospitals was collected using a self-designed questionnaire sent through WeChat from April 1 to 30, 2021. Chi-square test was used for statistical analysis. Results:A total of 126 questionnaires were distributed and 124 (124 baby-friendly hospitals) were withdrawn. There were 74 hospitals in the eastern, 18 in the central and 32 in the western region. Among the 124 hospitals, tertiary hospitals, general hospitals, and maternity and child care hospitals accounted for 72.6% ( n=90), 64.5% ( n=80) and 35.5% ( n=44), respectively. There were no significant differences in the hospital type, levels, EENC coverage and training, or implementation of mainly recommended EENC practices among the hospitals in the eastern, central and western regions (all P>0.05). The implementation rate of at least one mainly recommended EENC practice was 79.0% (98/124) and there was no significant difference in the implementation rates among eastern, central and western regions [86.4% (64/74), 13/18 and 65.6% (21/32), χ2=6.60, P=0.159]. A total of 80 (64.5%) hospitals implemented 10 or more recommended EENC practices, and the implementation rates in eastern, central and western regions were 71.6% (53/74), 10/18 and 53.1% (17/32), respectively ( χ2=4.08, P=0.130). Among the 17 mainly recommended measures of EENC, in eastern, central and western hospitals, the implementation rates were 10.8% (8/74), 2/18 and 18.8% (6/32) for mother-infant skin-to-skin contact for 90 min after birth; 66.2% (49/74), 11/18 and 68.8% (22/32) for delayed umbilical cord clamping; and 25.7% (19/74), 7/18 and 21.9% (7/32) for delayed routine care following skin-to-skin contact, respectively ( χ2=6.57, 0.34 and 4.53, all P>0.05). Conclusions:There is a big gap between the implementation of EENC in most baby-friendly hospitals in eastern, central and western China and the recommendation of the World Health Organization. It is necessary to further strengthen and standardize the implementation of EENC practices in baby-friendly hospitals in our country to continuously improve the health of newborns.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

【Objective】 To investigate the effect and mechanism of achyranthes bidentata polysaccharides （ABPS） on the differentiation of bone mesenchymal stem cells （BMSCs） into nucleus pulposus-like cells. 【Methods】 Five 4-week-old SD rats were sacrificed and their BMSCs were isolated and purified by repeated adherent method. The third-generation BMSCs were treated with different concentrations of ABPS for 48 h. The cell viability was detected by MTT method. The highest concentration of ABPS was selected for subsequent experiments. According to different treatment methods， cells were divided into control group （conventional culture）， ABPS group （200 mg/L of ABPS）， Notch1 group （transfected with Notch1）， Notch1 negative control group （transfected with Notch1 negative control）， and ABPS+Notch1 group （200 mg/L of ABPS was added after transfection with Notch1）. After 14 days of induction， the cell survival rate was measured by MTT method. CollagenⅡ was detected by immunohistochemical staining. The mRNA and protein expression levels of collagenⅡ， aggrecan， Notch1 and Hes1 were detected by qPCR and Western Blotting respectively. The glucosaminoglycan （GAG） was detected by alcian blue method on the 1st， 4th， 7th， 10th and 14th day of cell culture. 【Results】 After BMSCs were treated with 400 mg/L of ABPS for 48 h， the cell survival rate was significantly lower than that in the control group （P<0.05）. When the concentration was ≤200 mg/L， ABPS had no significant toxic effect on the growth of BMSCs. After 14 days of induction， compared with the control group， A value， GAG content in the medium， the expressions of collagen II and aggrecan mRNA and protein in the ABPS group were increased， and the expressions of Notch1 and Hes1 mRNA and protein were decreased （P<0.05）. The relative cell viability， GAG content in the medium， the expressions of collagen II and aggrecan mRNA and protein in the Notch1 group were decreased， and the expressions of Notch1 and Hes1 mRNA and protein were increased （P<0.05）. ABPS+Notch1 could partially reverse the inhibitory effect of Notch1 overexpression on the differentiation of BMSCs into nucleus pulposus-like cells. 【Conclusion】 ABPS can promote the differentiation of BMSCs into nucleus pulposus-like cells， and the mechanism may be related to the inhibition of Notch1 pathway.