To systematically synthesize evidence on multiple KRAS G12C inhibitors(KRAS G12C inhibitors, KRAS G12Ci) as monotherapy within a unified population and recommended-dose framework, establish a comparable benchmark range of efficacy and safety for previously treated patients with advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC), and explore potential effect modifiers.

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.

Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.

Objective:To explore the role and mechanism of Ras homolog gene family member E (RhoE) gene in myocardial fibrosis in diabetic cardiomyopathy.Methods:Wild-type SD rats were intraperitoneally injected with streptozotocin solution (STZ, 70 mg/kg) and an equal volume of sodium citrate solution to establish the type 1 diabetes mellitus (T1DM) group ( n=15) and the T1DM control group ( n=15), respectively. db/db spontaneous type 2 diabetes mellitus (T2DM) mice and wild-type C57BL/6J mice were conventionally housed for 8 weeks to establish the T2DM group ( n=5) and the T2DM control group ( n=5), respectively. Heterozygote SD rats with systemic knockout of the RhoE gene were intraperitoneally injected with STZ solution (70 mg/kg) and an equal volume of sodium citrate solution to establish the RhoE knockout T1DM group ( n=5) and the RhoE knockout control group ( n=5), respectively. Wild-type SD rats were injected with RhoE-overexpressing adeno-associated virus 9 through tail vein and intraperitoneally injected with STZ solution (70 mg/kg) to establish the RhoE overexpression T1DM group ( n=5), while wild-type SD rats injected with negative control virus through tail vein and intraperitoneally injected with an equal volume of sodium citrate solution served as the RhoE overexpression control group ( n=5). After successful modeling, all animals in each group were conventionally housed for an additional 6 or 8 weeks, which marked the experimental endpoint. At the experimental endpoint, echocardiography was performed to assess cardiac function of animals in each group, and left ventricular ejection fraction (LVEF) and the ratio of early to late diastolic transmitral flow velocity (E/A ratio) were analysed. Masson staining was used to detect collagen fiber deposition in myocardial tissue of animals in each group. Western blot analysis was conducted to detect the expression levels of RhoE gene, type Ⅰ collagen, type Ⅲ collagen, Smad2/3, and phosphorylated Smad2/3 protein in myocardial tissue of rats. Enzyme-linked immunosorbent assay was used to measure the levels of transforming growth factor-β1 (TGF-β1) in serum of rats. Results:Compared with their respective control groups, the expression of RhoE in the heart tissues of mice in the T2DM group and rats in the T1DM group was significantly downregulated, and the deposition of collagen fibers was more significant ( P<0.05), and LVEF and E/A ratio were lower (all P<0.05). Compared with the T1DM group, the phosphorylation level of Smad2/3、the levels of type Ⅰ collagen and type Ⅲ collagen in myocardial tissue and the level of TGF-β1 in serum were higher in the RhoE knockout T1DM group (all P<0.05). Additionally, rats in the RhoE overexpression T1DM group had higher LVEF and E/A ratios (both P<0.05) and less collagen fiber deposition ( P<0.05) compared with the T1DM group. Conclusions:Myocardial fibrosis induced by diabetes mellitus activates TGF-β1/Smads signaling pathway by inhibiting RhoE gene expression. Myocardial targeting overexpression of the RhoE mediated by adeno-associated virus 9 can alleviate myocardial fibrosis and improve cardiac function in rats with diabetic cardiomyopathy.

Objective To develop a toolkit suitable for assisting community health institutions in the early identification and inter-vention of mild cognitive impairment(MCI)among older adults.Methods A literature review was conducted to construct a draft of the identification and intervention toolkit.Tools with an expert approval rate above 70%were included after expert consultation.The final version of the toolkit was developed by integrating these tools with officially recommended tools in China.Results The expert consultation yielded an authority coefficient of 0.84.The finalized toolkit included the assessment tools of Mini-Mental State Examination,Montreal Cognitive Assessment,General Practitioner Assessment of Cognition,Cognitive Abilities Screening Instrument and Clock Drawing Test,and 18 intervention measures in-cluding pharmacological treatment,cognitive training and psychological interventions,etc.Conclusion The MCI Identification-Intervention Toolkit may serve as a reference for guiding the identification and inter-vention of MCI among older adults for community health institutions.

AIM:To investigate the impact of interleukin-17(IL-17D)knockout on lipid phagocytosis in ath-erosclerosis(AS)and bone marrow-derived macrophages.METHODS:Twenty 8-week-old ApoE-/-C57BL/6J mice were randomly assigned to experimental and control groups(10 mice per group).The experimental group was subjected to a high-fat diet for 8 weeks to induce AS,while the control group received a normal diet.Additionally,fifteen 8-week-old ApoE-/-IL-17D-/-and ApoE-/-mice were also fed a high-fat diet for the same duration.Body weight and blood lipid levels were measured.Aortas were harvested,and IL-17D expression was assessed using RT-qPCR.Bone marrow cells were iso-lated and differentiated into macrophages with colony-stimulating factors.Oil red O staining was employed to visualize lip-id deposition in aortic plaques and macrophages.To stimulate macrophages,oxidized low-density lipoprotein(oxLDL)was used,and RT-qPCR along with Western blot analyses were conducted to evaluate the expression of lipid phagocytosis-related genes and the p38 MAPK signaling pathway.Dehydrocorydaline(DHC),a p38 MAPK activator,was adminis-tered to IL-17D-/-macrophages,and the expression of CD36 and lipid phagocytosis were assessed.RESULTS:IL-17D ex-pression was significantly elevated in the aortas of AS mice and in oxLDL-treated macrophages(P<0.01).IL-17D-/-mice exhibited notably lower serum total cholesterol and low-density lipoprotein cholesterol levels(P<0.01),along with a sig-nificant reduction in plaque area in the aortas and aortic roots(P<0.01).Macrophages lacking IL-17D demonstrated de-creased expression of CD36,LOX-1,IL-1β,and IL-6(P<0.01)and showed diminished lipid phagocytosis.These mac-rophages also exhibited reduced phosphorylation of p38(P<0.01)compared to wild-type macrophages.Activation of p38 MAPK by DHC significantly countered the inhibitory effects of IL-17D knockout on CD36 expression(P<0.01)and en-hanced lipid phagocytosis in macrophages.CONCLUSION:Knockout of IL-17D may modulate lipid phagocytosis in macro-phages via the p38/CD36 signaling pathway,potentially inhibiting the formation and progression of aortic plaques in mice.

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.

Objective:To evaluate the effect of the degree of neuromuscular blockade on the intraoperative surgical conditions and postoperative recovery quality in patients undergoing lumbar interbody fusion.Methods:In this randomized controlled trial, 100 patients of either sex, aged 18-79 yr, with a body mass index of 18.5-35.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification < Ⅳ, scheduled for elective lumbar interbody fusion at the Affiliated Hospital of Xuzhou Medical University from August to October 2024, were allocated into 2 groups ( n=50 each) using stratified randomization based on the number of lumbar segments: deep neuromuscular blockade group (group D) and moderate neuromuscular blockade group (group M). The intraoperative post-tetanic count was maintained at 1 or 2 in group D, and the intraoperative train-of-four was maintained at 1 or 2 in group M. The scores for surgical conditions, duration of operation, blood loss, length of incision, occurrence of severe hypoxemia after extubation, requirement for rescue analgesia in post-anesthesia care unit, 15-item Quality of Recovery scale score and length of stay were recorded. Results:Compared with group M, the scores for surgical conditions were significantly increased, the rate of rescue analgesia in post-anesthesia care unit was decreased, 15-item Quality of Recovery scale scores were increased at 3 days after surgery ( P<0.05), and no significant changes were found in the duration of operation, blood loss, length of incision, incidence of severe hypoxemia after extubation and length of hospital stay in group D ( P>0.05). Conclusions:Compared with moderate neuromuscular blockade, deep neuromuscular blockade can provide better surgical conditions and improve the quality of early postoperative recovery for patients undergoing lumbar interbody fusion.

AIM:To investigate the impact of interleukin-17(IL-17D)knockout on lipid phagocytosis in ath-erosclerosis(AS)and bone marrow-derived macrophages.METHODS:Twenty 8-week-old ApoE-/-C57BL/6J mice were randomly assigned to experimental and control groups(10 mice per group).The experimental group was subjected to a high-fat diet for 8 weeks to induce AS,while the control group received a normal diet.Additionally,fifteen 8-week-old ApoE-/-IL-17D-/-and ApoE-/-mice were also fed a high-fat diet for the same duration.Body weight and blood lipid levels were measured.Aortas were harvested,and IL-17D expression was assessed using RT-qPCR.Bone marrow cells were iso-lated and differentiated into macrophages with colony-stimulating factors.Oil red O staining was employed to visualize lip-id deposition in aortic plaques and macrophages.To stimulate macrophages,oxidized low-density lipoprotein(oxLDL)was used,and RT-qPCR along with Western blot analyses were conducted to evaluate the expression of lipid phagocytosis-related genes and the p38 MAPK signaling pathway.Dehydrocorydaline(DHC),a p38 MAPK activator,was adminis-tered to IL-17D-/-macrophages,and the expression of CD36 and lipid phagocytosis were assessed.RESULTS:IL-17D ex-pression was significantly elevated in the aortas of AS mice and in oxLDL-treated macrophages(P<0.01).IL-17D-/-mice exhibited notably lower serum total cholesterol and low-density lipoprotein cholesterol levels(P<0.01),along with a sig-nificant reduction in plaque area in the aortas and aortic roots(P<0.01).Macrophages lacking IL-17D demonstrated de-creased expression of CD36,LOX-1,IL-1β,and IL-6(P<0.01)and showed diminished lipid phagocytosis.These mac-rophages also exhibited reduced phosphorylation of p38(P<0.01)compared to wild-type macrophages.Activation of p38 MAPK by DHC significantly countered the inhibitory effects of IL-17D knockout on CD36 expression(P<0.01)and en-hanced lipid phagocytosis in macrophages.CONCLUSION:Knockout of IL-17D may modulate lipid phagocytosis in macro-phages via the p38/CD36 signaling pathway,potentially inhibiting the formation and progression of aortic plaques in mice.

Objective To develop a toolkit suitable for assisting community health institutions in the early identification and inter-vention of mild cognitive impairment(MCI)among older adults.Methods A literature review was conducted to construct a draft of the identification and intervention toolkit.Tools with an expert approval rate above 70%were included after expert consultation.The final version of the toolkit was developed by integrating these tools with officially recommended tools in China.Results The expert consultation yielded an authority coefficient of 0.84.The finalized toolkit included the assessment tools of Mini-Mental State Examination,Montreal Cognitive Assessment,General Practitioner Assessment of Cognition,Cognitive Abilities Screening Instrument and Clock Drawing Test,and 18 intervention measures in-cluding pharmacological treatment,cognitive training and psychological interventions,etc.Conclusion The MCI Identification-Intervention Toolkit may serve as a reference for guiding the identification and inter-vention of MCI among older adults for community health institutions.