ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

Objective: To analyze the correlation between serum homocysteine (Hcy) and both folic acid (FA) and sperm DNA fragmentation index (DFI), so as to provide the evidence for male fertility assessment. Methods: Males who visited and measured the serum Hcy in the Reproductive Medicine Center of Huzhou Maternal and Child Health Care Hospital from September 2022 to September 2023 were selected as the study subjects. Sperm quality parameters and sperm DFI were analyzed by collecting sperm. Hcy and FA were measured by collecting venous blood. Participants were stratified into a high Hcy group (Hcy≥15.0 μmol/L) and a normal group (Hcy<15.0 μmol/L). The correlations between serum Hcy and FA and sperm DFI were evaluated using linear regression models. Results: A total of 173 participants were enrolled, including 39 in the high Hcy group and 134 in the normal group. The sperm concentration in the high Hcy group was significantly lower than that in the normal group [(91.77±61.11)×106/mL vs. (144.21±106.82)×106/mL, P<0.05]. No statistically significant differences were observed in semen volume, sperm motility, curvilinear velocity, straight-line velocity, average path velocity, or sperm morphology normal rate (all P>0.05). The FA level in the high Hcy group was lower than that in the normal group [(4.44±1.79) nmol/L vs. (7.64±3.68) nmol/L, P<0.05]. The sperm DFI in the high Hcy group was higher than that in the normal group [(19.21±8.85)% vs. (13.07±6.43)%, P<0.05]. Serum Hcy level showed a negative correlation with FA level (r=-0.369, P<0.05) and a positive correlation with sperm DFI (r=0.351, P<0.05). Conclusion Serum Hcy level is associated with sperm concentration, FA and sperm DFI, suggesting that serum Hcy may affect sperm quality.

Objective To explore the effect of nimodipine combined with minimally invasive puncture on neurological function,hemodynamics,and serum inflammatory factor levels in patients with hypertensive intracerebral hemorrhage(HICH).Methods A total of 108 patients with HICH treated at the Second Affiliated Hospital of Hebei North University from June 2019 to May 2022 were selected as the research subjects.They were divided into an observation group(n=55)and a control group(n=53)according to the treatment method.All patients in the two groups received minimally invasive puncture;on this basis,the patients in the observation group were treated with nimodipine for one month.The neurological deficit of patients in the two groups was evaluated by the National Institute of Health Stroke Scale(NIHSS)score before and after treatment.Before and after treatment,5 mL of fasting venous blood was taken from patients in the morning,and the serum was obtained by centrifugation.The serum levels of brain-derived neurotrophic factor(BDNF),neuron-specific enolase(NSE),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay.Ultrasonic transcranial Doppler blood flow analyzer was used to monitor the hemodynamic indexes such as mean blood flow velocity(Vm),resistance index(RI)and pulsitility index(PI)of patients in the two groups before and after treatment.The adverse reactions such as headache,dizziness,infection and rebleeding were recorded in the two groups after treatment.Results There was no statistically significant difference in the NIHSS score and serum NSE and BDNF levels between the two groups before treatment(P＞0.05).After treatment,the NIHSS score and serum NSE level of patients in the two groups were significantly lower than those before treatment,while the serum BDNF level was significantly higher than that before treatment(P＜0.05).After treatment,the NIHSS score and serum NSE level of patients in the observation group were significantly lower than those in the control group,while the serum BDNF level was significantly higher than that in the control group(P＜0.05).There was no statistically significant difference in the Vm,PI and RI between the two groups before treatment(P＞0.05).After treatment,the Vm and PI of patients in the two groups were significantly higher than those before treatment,while the RI was significantly lower than that before treatment(P＜0.05).After treatment,the Vm and PI of patients in the observa-tion group were significantly higher than those in the control group,while the RI was significantly lower than that in the control group(P＜0.05).There was no statistically significant difference in serum TNF-α,IL-6,and CRP levels between the two groups before treatment(P＞0.05).The levels of serum TNF-α,IL-6,and CRP of patients in the two groups after treatment were significantly lower than those before treatment(P＜0.05).After treatment,serum TNF-α,IL-6,and CRP levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of adverse reactions in patients in the control group and observation group was 7.55％(4/53)and 9.09％(5/55),respectively,and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Nimodipine combined with minimally invasive puncture can effectively improve the blood perfusion rate of HICH patients,reduce the degree of inflammatory response,and alleviate the patients'neurological function damage.

Objective To describe the clinical characteristics of acute dichlorvos poisoning and analyzed the risk factors affecting patient prognosis,in order to provide important treatment guidance and theoretical reference for reducing the mortality of patients with acute dichlorvos poisoning.Methods A retrospective study method was conduct to collect the clinical data of patients admitted to the department of emergency of Fuyang People's Hospital from November 2019 to November 2023 and analyze the clinical poisoning characteristics.The patients were divided into death group and survival group according to the prognosis to compare the differences in the clinical characteristics of patients with different outcomes.This study conducted binary multifactor Logistic regression analysis of statistically significant indicators to select the independent risk factors affecting the prognosis of patients,and drew the receiver operator characteristic(ROC)curve to predict value of the risk factors on the prognosis.Results In 82 patients,22(26.83%)died,39(47.56%)developed capillary leak syndrome(CLS),31(37.80%)had acute respiratory failure,and 35(42.68%)had shock.Compared with the survival group,patients in the death group were older(years:57.73±17.67 vs.44.25±13.74),the proportion of gastric lavage,cholinesterase activity,Glasgow coma scale(GCS),albumin,pH value were all significantly decreased[proportion of gastric lavage:81.82%(18/22)vs.100.00%(60/60),cholinesterase activity(U/L):235.96(200.00,401.67)vs.450.00(240.26,739.25),GCS scores:4.00(3.00,6.00)vs.12.00(4.00,15.00),albumin(g/L):39.35±12.02 vs.45.21±4.51,pH value:7.14(7.04,7.26)vs.7.38(7.28,7.40)],dichlorvos concentration,dipterex concentration,sequential organ failure assessment(SOFA),acute physiology and chronic health evaluationⅡ(APACHEⅡ),alanine transaminase(ALT),blood urea nitrogen(BUN),serum creatinine(SCr),MB isoenzyme of creatine kinase(CK-MB),blood lactate acid(Lac),and concurrent acute respiratory failure,shock,CLS ratio were significantly increased[dichlorvos concentration(μg/L):271.00(49.25,908.25)vs.64.00(16.75,211.00),dipterex concentration(μg/L):1 337.50(397.25,3 614.00)vs.494.00(71.00,1 679.80),SOFA score:12.50(9.00,15.50)vs.2.00(0.00,6.75),APACHEⅡscore:28.50(23.00,32.50)vs.6.50(2.25,19.00),ALT(U/L):40.40(17.28,66.33)vs.19.65(13.70,34.68),BUN(mmol/L):6.30±2.78 vs.5.05±1.48,SCr(μmol/L):87.59±39.67 vs.58.87±14.85,CK-MB(U/L):164.80(86.13,284.85)vs.116.05(81.65,160.60),Lac(mmol/L):3.00(1.68,9.15)vs.1.20(1.00,2.40),the proportion of concurrent acute respiratory failure:95.45%(21/22)vs.33.33%(20/60),proportion of concurrent shock:100.00%(22/22)vs.21.67%(13/60),proportion of concurrent CLS:95.45%(21/22)vs.30.00%(18/60)],the differences were statistically significant(all P<0.05).The binary multivariate Logistic regression analysis showed that age,SOFA score,and CLS were independent risk factors affecting the prognosis of dichlorvos poisoning[age:odds ratio(OR)=1.090,95%credibility interval(95%CI)was 1.019-1.167;SOFA score:OR=1.454,95%CI was 1.159-1.825;CLS:OR=122.473,95%CI was 7.954-1 885.787,all P<0.05].The ROC curve analysis shows that the age,SOFA score and CLS had a certain predictive value for the prognosis of patients with acute dichlorvos poisoning[area under the curve(AUC)were 0.752,0.864,0.827,95%CI were 0.622-0.881,0.767-0.960,0.735-0.919,the Youden index were 0.453,0.681,0.655,sensitivity were 63.6%,86.4%,95.5%,specific features were 81.7%,81.6%,70.0%,all P<0.05].Conclusions Age,SOFA score,and CLS are independent risk factors affecting the prognosis of patients with acute dichlorvos poisoning.In particular,CLS is the most important risk factor affecting the prognosis of patients.When managing acute dichlorvos poisoning,it is crucial to closely monitor the occurrence of CLS and administer prompt,proactive treatment.

Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.

Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.

BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.

Objective:To study the effects of fluoride on apoptosis and oxidative stress levels of spinal cord nerve cells in rats.Methods:A total of 54 6-week-old Sprague-Dawley female rats, weighing 150 - 200 g, were selected and fed for 1 week. They were divided into a control group [given deionized water containing 0 mg/L sodium fluoride (NaF)], a low fluoride group (given deionized water containing 50 mg/L NaF), and a high fluoride group (given deionized water containing 100 mg/L NaF) using a random number table method, with 18 rats in each group. All groups received standard feed. After 4, 8, and 12 weeks of fluoride exposure, six rats were selected from each group to observe the occurrence of dental fluorosis, and the motor function of hind limbs in rats was evaluated based on the Basso-Beattie-Bresnahan (BBB) score. Then the rats were anesthetized with 5% chloral hydrate via intraperitoneal injection and euthanized by cardiac puncture. Spinal cord tissue of the rats was collected to detect the activities of oxidative stress factors such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as the contents of malondialdehyde (MDA) and catalase (CAT). After 12 weeks of fluoride exposure, morphologic changes in rat spinal cord neurons were observed using Nissl staining, and apoptosis of spinal cord nerve cells was detected using the TdT mediated dUTP nick end labeling (TUNEL) cell apoptosis detection kit. The Western blotting was used to detect the expression of B-lymphoblastoma-2 (Bcl-2) gene related X protein (Bax), Bcl-2 promoter (Bad), and Bcl-2 protein in rat spinal cord tissue; immunofluorescence staining was used to observe the expression of Bax and Bcl-2 protein in spinal cord neurons.Results:After 12 weeks of fluoride exposure, rats in both the low fluoride and high fluoride groups developed varying degrees of dental fluorosis; the differences of BBB scores of rats in the control, low fluoride, and high fluoride groups were statistically significant ( F = 14.09, P < 0.001). The differences of SOD [(124.04 ± 4.87), (96.66 ± 15.01), (91.12 ± 15.87) U/mg prot] and GSH-Px activitives [(561.92 ± 59.65), (456.83 ± 29.51), (385.07 ± 74.87) U/mg prot], MDA [(9.96 ± 1.50), (16.64 ± 2.05), (20.80 ± 3.37) nmol/mg prot] and CAT contents [(8.97 ± 1.05), (6.39 ± 0.97), (6.42 ± 0.83) nmol/mg prot] among the control, low fluoride, and high fluoride groups were statistically significant ( F = 11.17, 14.19, 30.12, 14.52, P < 0.05). Among them, the SOD, GSH-Px activities, and CAT content in the low fluoride and high fluoride groups were lower than those in the control group, while the MDA content was higher than that in the control group ( P < 0.05). The GSH-Px activity in the high fluoride group was lower than that in the low fluoride group, and MDA content was higher than that in the low fluoride group ( P < 0.05). The intact neuronal structures and clear visible nuclei were seen, and Nissl bodies were uniformly stained in the spinal cord neurons of the control group rats, with more numbers, and no apoptotic cells were observed; the staining of Nissl bodies in the spinal cord neurons of rats was uneven in the low fluoride and high fluoride groups, with fewer numbers, and more apoptotic cells. There were statistically significant differences in the apoptosis rate of spinal cord nerve cells and the expression levels of Bax, Bad, and Bcl-2 protein in the spinal cord tissues of rats in the control, low fluoride, and high fluoride groups ( F = 272.81, 35.53, 17.57, 92.50, P < 0.05). The results of immunofluorescence staining showed that there were statistically significant differences in the fluorescent intensity of Bax and Bcl-2 proteins in the spinal cord neurons of rats in the control, low fluoride, and high fluoride groups ( F = 12.67, 22.14, P < 0.05). Conclusion:Chronic fluorosis induces a decrease in antioxidant enzyme activity, an increase in lipid peroxidation levels, and an increase in neuronal apoptosis in the spinal cord of rats.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.