Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

Objective To compare the application value of three image post-processing techniques volume rendering(VR),multiplanar reformation(MPR)and curved planar reformation(CPR)in the identifi-cation of rib fracture malunion.Methods The types and numbers of rib fracture malunion in 75 pa-tients were recorded,and the sensitivity,specificity,accuracy and Youden index of VR,MPR and CPR in the diagnosis of rib fracture malunion were compared.Receiver operator characteristic(ROC)curve was drawn and area under the curve(AUC)was calculated,and the detection rates of three image post-processing techniques for different types of rib fracture malunion were compared.Results A total of 243 rib fractures were malunion in 75 patients.The diagnostic sensitivity of VR,MPR and CPR for rib fracture malunion was 52.67%,79.84%and 91.36%,the specificity was 99.58%,97.89%and 99.15%,the accuracy was 83.66%,91.76%and 96.51%,the Youden index was 0.52,0.78 and 0.91,the AUC was 0.761,0.889 and 0.953,respectively.Compared with VR,there were statistically signifi-cant differences in the number of broken rib end misalignment over 1/3,broken rib end overlap,bro-ken rib end angulation and intercostal bridge detected in MPR(P<0.05).Compared with VR,there was a statistically significant difference in the number of different types of rib fracture malunion de-tected by CPR(P<0.05).Compared with MPR,there were statistically significant differences in the number of broken rib end misalignment over 1/3,broken rib end separation and intercostal bridge de-tected in CPR(P<0.05).Conclusion The three image post-processing techniques are of great signifi-cance for the identification of rib fracture malunion.Especially CPR is highly effective in the diagno-sis of rib fracture malunion,and can be used as the main post-processing technique for forensic clini-cal identification of rib fracture malunion.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

Objective:To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma(MM)bone disease(MBD)patients with different blood separation results.Methods:A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group[119 cases,serum,colloid and red blood cell(RBC)from top to bottom of sample]and abnormal group(15 cases,serum,mixed layer of RBC and serum,colloid and RBC from top to bottom of sample)according to the results of blood separation.According to the imaging findings,MBD was classified into grade 0-4,grade 0-2 was mild,and grade 3-4 was severe.The MBD grade of patients in the two groups was analyzed.The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated.The correlation between β 2-microglobulin(MG)and bone metabolic indexes was analyzed by Pearson correlation analysis.Results:In the control group,there were 69 cases of grade 0-2 and 50 cases of grade 3-4,while in the abnormal group,there were 5 cases of grade 0-2 and 10 cases of grade 3-4,the difference was statistically significant(P＜0.05).The serum β 2-MG,β-CTX levels in abnormal group were both significantly higher than those in control group,while the levels of P1NP and osteocalcin(OC)were significantly lower(all P＜0.001).In the control group,there were 95 patients with ≥ partial response(PR)and the blood separation results were not changed,while 24 patients with＜PR and 5 of them had abnormal blood separation results.In the abnormal group,9 patients with efficacy≥PR showed normal blood separation results,while 6 patients with efficacy＜PR and 5 of them still remained abnormal blood separation results.Compared with before treatment,β-CTX and β 2-MG of patients with efficacy ≥ PR were significantly decreased but P1NP and OC increased in the control group(all P＜0.00 1),which was the same as abnoraml group(both P＜0.001,P＜0.01).There were no significant changes in the levels of all indexes in the two groups of patients with efficacy＜PR(P＞0.05).Compared with before treatment,the levels of β-CTX and β 2-MG in the control group with unchanged blood separation results were significantly decreased(both P＜0.00l),while the levels of P1NP and OC were significantly increased(P＜0.01,P＜0.001),and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change(P＞0.05);the levels of β-CTX and β 2-MG in the abnormal group transformed to normal blood separation result were significantly decreased(both P＜0.01),while the levels of P1NP and OC were significantly increased(P＜0.001,P＜0.01),and the level of each index in patients with unchanged blood separation results did not significantly change(P＞0.05).Pearson correlation analysis showed that serumβ 2-MG was positively correlated with β-CTX(r=0.709,P＜0.001),and negatively correlated with P1NP and OC(r=-0.410,r=-0.412,both P＜0.001).Conclusion:MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis,which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels,leading to more serious bone metabolic homeostasis disorder.The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition,efficacy monitoring and prognosis evaluation of MBD patients.

Objective:To investigate age-related characteristics of gait parameters in the elderly.Methods:From February 2023 to August 2023, a convenient sampling method was used to investigate the elderly over 60 years old in communities in Beijing.General characteristics and anthropometric data were collected.Gait parameters of the subjects during normal speed walking were measured using a wearable gait analyzer.Comparisons were made of the basic characteristics, physical status and gait parameters in different age groups.Linear regression analysis was used to evaluate the changes of physical status and gait parameters with age, with the 60-69-year-old group as the baseline standard.Results:A total of 670 elderly people were included, including 324(48.4%)aged 60-69 years, 285(42.5%)aged 70-79 years, and 61(9.1%)aged ≥80 years.Linear regression analysis showed that after adjusting for confounding factors, with increasing age, skeletal muscle mass index(SMI)( β=-0.018, 95% CI: -0.029--0.007), calf circumference( β=-0.096, 95% CI: -0.142--0.051), upper limb flexibility( β=-0.200, 95%, 95% CI: -0.355--0.046), lower limb flexibility( β=-0.244, 95% CI: -0.377--0.111), grip strength( β=-0.397, 95% CI: -0.491--0.303), the Short Physical Performance Battery(SPPB)( β=-0.080, 95% CI: -0.100--0.060)decreased( P<0.05), and the gait parameter such as speed( β=-0.010, 95% CI: -0.014--0.007), cadence( β=-0.398, 95% CI: -0.634--0.162), step length/height( β=-0.002, 95% CI: -0.003--0.002), stride length( β=-0.009, 95% CI: -0.011--0.007), swing power( β=-0.009, 95% CI: -0.012--0.006), ground impact( β=-0.020, 95% CI: -0.026--0.014), foot fall( β=-0.050, 95% CI: -0.064--0.036), pre-swing angle( β=-0.545, 95% CI: -0.714--0.377)all decreased( P<0.05), while stride time( β=0.005, 95% CI: 0.001-0.009), single limb support time( β=1.566, 95% CI: 0.499-2.633), terminal double limb support time( β=0.609, 95% CI: 0.084-1.134), swing duration( β=1.288, 95% CI: 0.024-2.552), single step time( β=2.417, 95% CI: 0.462-4.372)and support phase time( β=1.935, 95% CI: 0.421-3.449)all increased( P<0.05). Conclusions:The walking ability tends to decline with age in older people in the community who walk at a normal walking speed.

Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P＜0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.

【Objective】 To analyze the situation of regular whole blood donation in Tianjin between 2013 and 2022, in order to provide data support for improving the recruitment and retention measures of regular blood donors and ensuring safe clinical blood supply. 【Methods】 From 2013 to 2022, 185 639 regular whole blood donors in Tianjin were selected as the study group and 1 015 312 other whole blood donors in the same period were selected as the control group. The demographic data, blood collection volume and blood retest screening of blood donors in the two groups were statistically analyzed. 【Results】 The number of regular blood donors and the volume of blood donated in Tianjin increased year by year from 2013 to 2022, with an average annual growth rate of 6.22% and 6.18%, respectively. From 2013 to 2021, the retention rate of regular blood donors increased first and then decreased. The proportion of male blood donors in the study and control groups showed a decreasing trend but the proportion of female donors showed an increasing trend, with the proportion of male donors in the study group higher than that in the control group and the proportion of female donors lower than that in the control group (both P<0.05). In the study group, the majority of blood donors were in the age of 26-35 years old, followed by those of 36-45 years old; in the control group, the majority of blood donors were in the age of 18-25 years old, followed by those of 26-35 years old; the proportion of blood donors in the study group in the age of 18-25 years old was lower than that in the control group, while the proportion of blood donors of other age group was higher than that in the control group, and the difference was statistically significant (P<0.05). The rates of 200 mL and 300 mL blood donations and insufficient blood donations in the study group were lower than those in the control group, while the rate of 400 mL blood donations was higher than that in the control group, and the differences were statistically significant. Among the blood donors in the study group, the proportion of students, civil servants, medical workers, military personnel, teachers and others was lower than that of the control group, while the proportion of the rest occupations was higher in the study group than that of the control group, and the differences were all statistically significant. There was a significant difference in the proportion of regular blood donors among blood donors of different professions. The re-test deferral rates of ALT and anti-TP in the study group showed a decreasing trend followed by an increasing trend, and the re-test deferral rates of HBV, HCV and HIV showed an increasing trend followed by a decreasing trend, and all the re-test deferral rates in the study group were lower than those in the control group, and the differences were statistically significant (P<0.05) . 【Conclusion】 From 2013 to 2022, the situation of regular blood donors in Tianjin has a certain regularity, and there is certain room for growth. Precise recruitment strategies targeting different populations should be adopted to have more regular blood donors.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.