In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.

AIM:This study aims to explore the effects and underlying mechanisms of caloric restriction(CR)on folic acid(FA)-induced acute kidney injury(AKI)in mice.METHODS:An AKI model was established by in-traperitoneal injection of FA(250 mg/kg).(1)Twenty male C57BL/6J mice(20～25 g)were randomly assigned to 4 groups(n=5):sham+ad libitum(AL),FA+AL,sham+CR,and FA+CR.The mice in CR groups were subjected to a 66%reduction in daily food intake within a limited feeding window for 2 weeks,while those in AL groups had unrestricted access to food.All mice had free access to water,and their body weight changes were monitored throughout the experi-ment.(2)An additional set of twenty male C57BL/6J mice were divided into 4 groups(n=5):control,A769662,FA,and FA+A769662.The AMP-activated protein kinase(AMPK)agonist A769662(30 mg/kg)was administered intraperito-neally for 3 d prior to FA injection.(3)Modeling of tubule-specific AMPK knockout(RT-AMPK-CKO)mice followed the same protocol as wild-type C57BL/6J mice.Blood and kidney tissues were harvested 48 h after FA injection.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were measured using an automatic biochemical analyzer.The kidney pa-thology was examined by HE staining.The malondialdehyde(MDA)level and the reduced/oxidized glutathione(GSH/GSSG)ratio were assessed using assay kits.The protein levels of p-AMPK,AMPK,and ferroptosis-related markers were evaluated by Western blot and immunohistochemistry.RESULTS:(1)After 2 weeks,CR significantly reduced body weight and increased p-AMPK level compared with AL group(P<0.05).(2)Compared with FA+AL group,the mice in FA+CR and FA+A769662 groups exhibited notably lowered SCr and BUN levels,reduced expression of kidney injury mole-cule-1 and neutrophil gelatinase-associated lipocalin,lowered tubular injury scores,decreased long-chain fatty acid-CoA ligase 4(FACL4)and 4-hydroxynonenal levels,restored glutathione peroxidase 4(GPX4)expression,decreased MDA level,and enhanced GSH/GSSG ratio(P<0.05).(3)In the FA-induced renal injury model,RT-AMPK-CKO mice showed no significant differences compared with wild-type mice(P>0.05).However,in the FA+CR model,RT-AMPK-CKO mice failed to exhibit renal protection,with increased lipid peroxidation,elevated MDA level,and reduced GSH/GSSG ratio(P<0.05).Furthermore,CR-induced down-regulation of FACL4 and up-regulation of GPX4 were significantly reversed in RT-AMPK-CKO mice(P<0.05).CONCLUSION:The CR attenuates FA-induced AKI in mice by activating AMPK and inhibiting ferroptosis.

In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.

AIM:This study aims to explore the effects and underlying mechanisms of caloric restriction(CR)on folic acid(FA)-induced acute kidney injury(AKI)in mice.METHODS:An AKI model was established by in-traperitoneal injection of FA(250 mg/kg).(1)Twenty male C57BL/6J mice(20～25 g)were randomly assigned to 4 groups(n=5):sham+ad libitum(AL),FA+AL,sham+CR,and FA+CR.The mice in CR groups were subjected to a 66%reduction in daily food intake within a limited feeding window for 2 weeks,while those in AL groups had unrestricted access to food.All mice had free access to water,and their body weight changes were monitored throughout the experi-ment.(2)An additional set of twenty male C57BL/6J mice were divided into 4 groups(n=5):control,A769662,FA,and FA+A769662.The AMP-activated protein kinase(AMPK)agonist A769662(30 mg/kg)was administered intraperito-neally for 3 d prior to FA injection.(3)Modeling of tubule-specific AMPK knockout(RT-AMPK-CKO)mice followed the same protocol as wild-type C57BL/6J mice.Blood and kidney tissues were harvested 48 h after FA injection.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were measured using an automatic biochemical analyzer.The kidney pa-thology was examined by HE staining.The malondialdehyde(MDA)level and the reduced/oxidized glutathione(GSH/GSSG)ratio were assessed using assay kits.The protein levels of p-AMPK,AMPK,and ferroptosis-related markers were evaluated by Western blot and immunohistochemistry.RESULTS:(1)After 2 weeks,CR significantly reduced body weight and increased p-AMPK level compared with AL group(P<0.05).(2)Compared with FA+AL group,the mice in FA+CR and FA+A769662 groups exhibited notably lowered SCr and BUN levels,reduced expression of kidney injury mole-cule-1 and neutrophil gelatinase-associated lipocalin,lowered tubular injury scores,decreased long-chain fatty acid-CoA ligase 4(FACL4)and 4-hydroxynonenal levels,restored glutathione peroxidase 4(GPX4)expression,decreased MDA level,and enhanced GSH/GSSG ratio(P<0.05).(3)In the FA-induced renal injury model,RT-AMPK-CKO mice showed no significant differences compared with wild-type mice(P>0.05).However,in the FA+CR model,RT-AMPK-CKO mice failed to exhibit renal protection,with increased lipid peroxidation,elevated MDA level,and reduced GSH/GSSG ratio(P<0.05).Furthermore,CR-induced down-regulation of FACL4 and up-regulation of GPX4 were significantly reversed in RT-AMPK-CKO mice(P<0.05).CONCLUSION:The CR attenuates FA-induced AKI in mice by activating AMPK and inhibiting ferroptosis.

Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Objective:To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection.Method:Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis.Results:The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population ( P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion:Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Objective To investigate the role and mechanism of growth differentiation factor (GDF) 15 in ischemia-reperfusion injury (IRI) during kidney transplantation. Methods Nine wild type donor mice and 9 wild type recipient mice were selected. The renal graft of 3 recipient mice were harvested at 4, 24 and 72 h after transplantation. GDF family transcriptome analysis was carried out, and the expression of GDF15 in renal tissues of each group were detected. Five wild type donor mice, 5 GDF15 knockout donor mice and 10 wild type recipient mice were selected. According to the experimental scheme, the mice were divided into wild type sham operation group, wild type transplantation group, GDF15 knockout sham operation group and GDF15 knockout transplantation group. Serum and renal tissue samples were extracted 72 h after transplantation. The renal function, renal tubular injury, inflammatory cell infiltration, inflammatory factors, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB expression level were compared in each group. Nine wild type donor mice, 9 GDF15 knockout donor mice and 18 wild type recipient mice were selected. According to the experimental scheme, the mice were divided into wild type transplantation group and GDF15 knockout transplantation group, and the survival rate of two group after kidney transplantation was observed. Results Transcriptome sequencing of renal graft tissues indicated that GDF15 was the most up-regulated GDF family gene, which was mainly expressed in renal tubules. Compared with the sham operation group, the renal function of mice was declined in the transplantation group. Compared with the wild type transplantation group, the serum creatinine and blood urea nitrogen levels of mice were significantly up-regulated in the GDF15-knockout transplantation group (both P < 0.05). The 1-week survival rate of mice was 87.6% in the wild type transplantation group and 41.8% in the GDF15 knockout transplantation group. In the GDF15 knockout transplantation group, the expression level of kidney injury molecule (KIM)-1 was up-regulated, and the renal tubule injury score was increased. In the wild type transplantation group, the renal tubules were dissolved or necrotized, and tubular formation was seen in the extramedullary and cortex area, whereas tubular necrosis and tubular formation were more evident in the GDF15 knockout transplantation group. The expression levels of myeloperoxidase (MPO) and F4/80 were up-regulated in the transplantation group, and the inflammatory cell infiltration was aggravated in the GDF15 knockout transplantation group. Compared with the sham operation group, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the transplantation group were up-regulated. Compared with the wild type transplantation group, the expression levels of TNF-α, IL-1β and IL-6 were also up-regulated in the GDF15 knockout transplantation group (all P < 0.05). In the transplantation group, the expression levels of TLR4 and NF-κB in the renal graft tissues were higher than those in the sham operation group. In the GDF15 knockout transplantation group, the expression levels of TLR4 and NF-κB in the renal graft tissues were higher compared with those in the wild type transplantation group. Conclusions GDF15 may alleviate the IRI of renal graft probably via inhibiting the TLR4-NF-κB signaling pathway.

Kidney transplantation is more efficacious compared with other organ transplantations. Nevertheless, postoperative complications, such as renal ischemia-reperfusion injury (IRI), severely affect the survival rate and quality of life of recipients. How to mitigate the IRI of renal allografts has become one of the key topics in the field of kidney transplantation. At present, ischemic preconditioning enables renal allografts to adapt to ischemia, which is one of the effective methods to prevent the progression of IRI. However, the underlying mechanism remains elusive. In this article, the application of ischemic preconditioning in IRI, the regulation mechanism of ischemic preconditioning on the IRI of renal allografts at the cellular level and intracellular signaling pathway, and clinical application value and prospect of ischemic preconditioning were reviewed, aiming to provide reference for alleviating the IRI of renal allografts, enhancing the survival rate of the recipients and renal allografts and improving the quality of life of recipients.