Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective:To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. Methods:A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c. 548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion:Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.

Objective To understand the prevalence status quo of mild cognitive impairment(MCI)in the elderly people by conducting the investigation on the elderly people in somewhere,and to explore the influ-encing factors of MCI in the elderly people to provide reference for constructing the MCI localized computer screening and diagnosis system in the elderly.Methods A multi-stage sampling method was used to deter-mine the survey population.The self-made questionnaires,mini mental state examination(MMSE),geriatric depression screening scale(GDS-15),geriatric anxiety screening scale,geriatric psychiatric symptoms scale,and daily living ability scale were used to collect or evaluate basic information,cognitive impairment,depres-sion,anxiety,psychiatric symptoms,and daily living ability of elderly people from March 5,2022 to July 22,2022.The index system affecting MCI was screened by the receiver operating characteristic(ROC)curve and unconditional binary logistic regression,and the localized computer screening diagnosis system was construc-ted.Results A total of 1 004 elderly individuals were surveyed,among them there were 262 cases(26.1％)of MCI,194 cases(19.3％)of anxious state,21 cases(2.1％)of depression,313 cases(31.2％)of psychotic symptoms and 32 cases(3.2％)of impaired ability of activities of daily living(ADL).The ROC curve analysis showed that the area under the curves(AUC)of depression,anxiety and psychotic symptoms for predicting MCI in elderly individuals were 0.640,0.645,and 0.586,respectively.AUC of anxiety combined with depres-sion(anxiety+depression),depression+psychotic symptoms,anxiety+psychotic symptoms and depression+anxiety+psychotic symptoms were 0.676,0.652,0.645 and 0.676,respectively.The multivariate analysis found that the age,whether or not anyone close to you died in the last two years,ability of activities of daily living,anxiety degree,whether or not having psychotic symptoms,education level,whether or not having joint habitation with the family members and suffering from multiple chronic diseases were the influencing factors of MCI.Conclusion The age,education level,death of close persons in the past two years,ability to live daily life,depression,and psychotic symptoms could serve as the indicators system of the MCI localized computer screening and diagnosis system.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

This study was aimed at characterizing the variations in hemagglutinin(HA)and neuraminidase(NA)genes of influenza virus subtype A(H1N1)pdm09 isolated during the 2022-2023 influenza monitoring year in Shandong Province,to provide a scientific basis for influenza prevention and control.A total of 14 A(H1N1)pdm09 subtype influenza strains were se-lected randomly by city by the influenza monitoring network laboratory.The vaccine strains recommended by the WHO served as references for whole gene sequencing analysis.A fluorescence method was used to conduct neuraminidase inhibition experi-ments to evaluate drug sensitivity.The A(H1N1)pdm09 influenza virus in Shandong Province,2022-2023 belonged to the 5a.2a evolutionary cluster in the 6B.1A branch.Nucleotide sequence analysis indicated that the HA and NA genes were closely re-lated to the Northern Hemisphere vaccine strain A/Victoria/2570/2019 in the years 2021-2023,and showed homology of 98.5％to 98.7％and 98.8％to 99.1％,respectively.Amino acid sequence analysis revealed 20 amino acid sequence mutations in the HA protein,but only one virus strain was found to have antigen drift,and three virus strains showed loss of HA protein glycosylation sites.No mutations were found at important sites affecting NA enzymes.The neuraminidase inhibition experiment indicated viral sensitivity to anti-influenza drugs.In conclusion,the monitored virus strains had high overall homology with vac-cine strains but showed some amino acid variation.In the future,continued monitoring of the genetic variation characteristics of influenza viruses will be necessary to understand the risk of influenza epidemics,and the effectiveness of influenza vaccines and therapeutic drugs.

This study was aimed at understanding the pollution distribution pattern of avian influenza virus in the environ-ment in poultry related places in Shandong Province,to provide a scientific basis for the prevention,control,prediction,and early warning regarding human infection with avian influenza.From 2020 to 2023,6 523 environmental samples were collected in 16 cities in Shandong Province from four types of poultry-related places.Fluorescence quantitative PCR was used for nucleic acid testing of influenza A virus.Positive samples were further identified for the H5,H7,and H9 subtypes of avian influenza virus.The epidemiological characteristics of avian influenza viruses in the poultry related environment of Shandong Province were described,and inter-rate comparisons were performed with the x2 test.During 2020-2023,6 523 environmental samples were collected,and 1 007 cases positive for avian influenza virus were detected,with a positivity rate of 15.44％.H5,H7,and H9 subtypesand mixed infections were detected.H9 was the main subtype(88.48％)in positive specimens.A significant difference in positivity rates was observed among regions(x2=431.956,P＜0.001),and the highest positivity rate was 28.93％.Significant differences in positivity rates were observed among monitoring sites(x2=304.604,P＜0.001),sample types(x2=109.678,P＜0.001),and quarters(x2=64.963,P＜0.001).The positive detection rate was highest at monitoring sites in urban and rural live poultry markets(20.12％),and the positive detection rate of samples collected by wiping meat cut-ting board surfaces was higher than that of other samples(22.56％).The peak positive detection rate occurred in spring(20.31％).Widespread contamination with avian influenza virus was observed in poultry environments in Shandong Prov-ince.The H9 subtype,the main pathogen,coexisted with H5 and H7 subtypes,thus posing a risk of human infection with avian influenza.Therefore,prevention and control of avian influenza must be strengthened in key seasons,areas,places,and links.

Objective To investigate the clinical efficacy of Guiyuan Shujin Mixture in the treatment of patients with lumbar disc herniation(LDH)and to explore its possible therapeutic mechanism.Methods Sixty-eight patients with LDH of qi stagnation and blood stasis syndrome were randomly divided into trial group and control group,with 34 cases in each group.The control group was treated with Celecoxib Tablets and Mecobalamin Tablets orally,and the trial group was treated with Guiyuan Shujin Mixture on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.Before and after treatment,the two groups were observed in the changes of the Visual Analogue Scale(VAS)score of low back pain and lower limb pain,Oswestry Disability Index(ODI)score,modified Japanese Orthopedic Association(JOA)score,serum levels of inflammatory factors of tumor necrosis factor α(TNF-α),interleukin 6(IL-6)and interleukin 1β(IL-1β),and serum nuclear factor-κB p65(NF-κB p65)level.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,one case fell off in the trial group and 3 cases fell off in the control group.Eventually,33 cases in the trial group and 31 cases in the control group were included for the efficacy statistics.(2)After 4 weeks of treatment,the total effective rate of the trial group was 96.97%(32/33),and that of the control group was 87.10%(27/31).The intergroup comparison(tested by rank sum test)showed that the curative effect of the trial group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the VAS score and ODI score of low back pain and lower limb pain in the two groups were lower than those before treatment(P＜0.05 or P＜0.01),and the modified JOA score was higher than that before treatment(P＜0.01).The decrease of VAS score and ODI score of low back pain and lower limb pain and the increase of modified JOA score in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(4)After treatment,the serum levels of inflammation-related indicators of TNF-α,IL-6,IL-1β and NF-κB p65 in the two groups were lower than those before treatment(P＜0.01),and the decrease in the trial group was significantly superior to that in the control group(P＜0.01).(5)During the treatment,the incidence of adverse events in the trial group was 2.94%(1/34)and that in the control group was 8.82%(3/34),and the difference between the two groups was not significant(P＞0.05).Conclusion Guiyuan Shujin Mixture exerts certain effect in the treatment of LDH patients with qi stagnation and blood stasis syndrome.It can effectively relieve the pain symptoms of patients,improve the lumbar function of patients,and reduce the expression levels of serum inflammatory factors and NF-κB p65.The mechanism may be related with the decrease of the level of inflammatory factors and with the inhibition of the activation of NF-κB signaling pathway.