Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

Background Regulatory interactions between microRNAs (miRNAs) and messenger RNAs (mRNAs) are involved in the progression of pulmonary fibrosis, which can either promote or inhibit the development of this disease. Objective To explore the miRNA-mRNA regulatory network during the progression of silica (SiO₂)-induced pulmonary fibrosis in mice using integrated mRNA-seq and miRNA-seq analysis. Methods A mouse model of pulmonary fibrosis was established by dynamic SiO₂ dust exposure. The experimental design included a blank control group and four SiO₂-exposed groups (7, 14, 28, and 56 d, n=10 per group). Successful model induction was confirmed by histopathological analysis (HE and Masson staining), hydroxyproline (HYP) quantification, and expression of key fibrosis-related cytokines [fibroblast growth factor (FGF), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α)]. Lung tissues from mice in each group were subjected to sequencing, and Mfuzz was used for time-series gene clustering to identify dynamic progression patterns. DESeq2 was utilized to identify differentially expressed genes (DEGs) and differentially expressed miRNAs. Enrichment analysis of DEGs was performed to identify critical signaling pathways and biological processes underlying pulmonary fibrosis progression. Expression of four selected miRNAs was subsequently validated by real-time quantitative polymerase chain reaction (RT-qPCR). The target mRNAs of key miRNAs were comprehensively predicted by integrating miRBase, starBase, and miRTarBase to construct the regulatory networks and investigate potential functions. Results SiO₂ exposure led to time-dependent aggravation of pulmonary fibrosis in mice, evidenced by increased fibrous deposition, elevated HYP levels (P < 0.01), and up-regulation of four kinds of pro-fibrotic cytokines (P < 0.01) compared with the NT group. Mfuzz clustering revealed the stage-specific characteristics. Compared to controls, 231, 662, 448, and 1020 DEGs were identified after SiO₂ exposure at 7, 14, 28, and 56 d, respectively, primarily enriched in immune responses and chemokine signaling. During critical fibrotic phases—7 d (acute inflammation and initiation) and 28 d (chronic inflammation and establishment)—18 differentially expressed miRNAs were identified; notably mmu-miR-135b-5p was significantly dysregulated at both time points. The expression trends of the four key miRNAs (mmu-miR-135b-5p, mmu-miR-708-5p, mmu-miR-21a-3p, and mmu-miR-205-5p) were consistent with the sequencing results. Furthermore, bioinformatics databases were used to predict the target mRNAs of key miRNAs. The constructed network highlighted critical miRNA-mRNA pairs—including mmu-miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, mmu-miR-205-5p and Ereg which were closely associated with inflammatory response, extracellular matrix deposition, and fibroblast activation. Conclusion The progression of pulmonary fibrosis is accompanied by dynamic changes in miRNA-mRNA regulatory networks. The identified miRNA-target axes (e.g., miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, and mmu-miR-205-5p and Ereg—) may play important roles in fibrogenesis and provide potential therapeutic targets for pulmonary fibrosis.

Background Regulatory interactions between microRNAs (miRNAs) and messenger RNAs (mRNAs) are involved in the progression of pulmonary fibrosis, which can either promote or inhibit the development of this disease. Objective To explore the miRNA-mRNA regulatory network during the progression of silica (SiO₂)-induced pulmonary fibrosis in mice using integrated mRNA-seq and miRNA-seq analysis. Methods A mouse model of pulmonary fibrosis was established by dynamic SiO₂ dust exposure. The experimental design included a blank control group and four SiO₂-exposed groups (7, 14, 28, and 56 d, n=10 per group). Successful model induction was confirmed by histopathological analysis (HE and Masson staining), hydroxyproline (HYP) quantification, and expression of key fibrosis-related cytokines [fibroblast growth factor (FGF), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α)]. Lung tissues from mice in each group were subjected to sequencing, and Mfuzz was used for time-series gene clustering to identify dynamic progression patterns. DESeq2 was utilized to identify differentially expressed genes (DEGs) and differentially expressed miRNAs. Enrichment analysis of DEGs was performed to identify critical signaling pathways and biological processes underlying pulmonary fibrosis progression. Expression of four selected miRNAs was subsequently validated by real-time quantitative polymerase chain reaction (RT-qPCR). The target mRNAs of key miRNAs were comprehensively predicted by integrating miRBase, starBase, and miRTarBase to construct the regulatory networks and investigate potential functions. Results SiO₂ exposure led to time-dependent aggravation of pulmonary fibrosis in mice, evidenced by increased fibrous deposition, elevated HYP levels (P < 0.01), and up-regulation of four kinds of pro-fibrotic cytokines (P < 0.01) compared with the NT group. Mfuzz clustering revealed the stage-specific characteristics. Compared to controls, 231, 662, 448, and 1020 DEGs were identified after SiO₂ exposure at 7, 14, 28, and 56 d, respectively, primarily enriched in immune responses and chemokine signaling. During critical fibrotic phases—7 d (acute inflammation and initiation) and 28 d (chronic inflammation and establishment)—18 differentially expressed miRNAs were identified; notably mmu-miR-135b-5p was significantly dysregulated at both time points. The expression trends of the four key miRNAs (mmu-miR-135b-5p, mmu-miR-708-5p, mmu-miR-21a-3p, and mmu-miR-205-5p) were consistent with the sequencing results. Furthermore, bioinformatics databases were used to predict the target mRNAs of key miRNAs. The constructed network highlighted critical miRNA-mRNA pairs—including mmu-miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, mmu-miR-205-5p and Ereg which were closely associated with inflammatory response, extracellular matrix deposition, and fibroblast activation. Conclusion The progression of pulmonary fibrosis is accompanied by dynamic changes in miRNA-mRNA regulatory networks. The identified miRNA-target axes (e.g., miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, and mmu-miR-205-5p and Ereg—) may play important roles in fibrogenesis and provide potential therapeutic targets for pulmonary fibrosis.

Despite significant advances in the field of critical care medicine over the past three decades, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) remains the primary temporary mechanical circulatory support modality for patients with acute severe circulatory failure. With the accumulation of clinical experience and the increasing maturity of operational techniques in V-A ECMO, its technical management—particularly hemodynamic management—has become a key factor influencing patient outcomes. To further improve patient survival, the Chinese Critical Care Ultrasound Study Group, in collaboration with the Hemodynamic Therapy of Critical Care Collaborative Group and the Critical Care Medicine Branch of the China International Exchange and Promotive Association for Medical and Health Care, organized experts in critical care medicine to develop the Consensus on Hemodynamic Management in Adult Veno-Arterial Extracorporeal Membrane Oxygenation (2026 Edition). Based on years of clinical experience and the latest evidence-based medical evidence, this consensus formulates 15 systematic recommendations covering the entire process of V-A ECMO, including initiation, management during support, and weaning, aiming to promote standardized application of hemodynamic management in V-A ECMO.

Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

Objective: To understand the current status of psychological sub health among secondary vocational school students and explore its related factors, so as to provide a scientific basis for improving their mental health. Methods: From September to December 2024, a convenience sampling method was used to conduct a questionnaire survey among 5 141 secondary vocational school students from 16 schools across 8 provinces and municipalities (Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai, Zhejiang). A self designed questionnaire was used to collect data on students demographic characteristics and lifestyle behaviors. The Multidimensional Sub health Questionnaire of Adolescents was adopted to assess psychological sub health status. Multivariate binary Logistic stepwise regression analysis was performed to explore the related factors of psychological sub health among secondary vocational school students. Results: The detection rate of psychological sub health among secondary vocational school students was 11.0%, with detection rates of emotional problems, conduct problems, and social adaptation difficulty being 12.3 %, 12.5%, and 9.5%, respectively. Logistic regression analysis revealed that boys and students whose fathers had an educational level of primary school or below, and junior high school, had relatively lower risks of developing psychological sub health or emotional problems, conduct problems, and social adaptation difficulty ( OR =0.55-0.64, all P <0.05). Conversely, students with urban household registration, those with left behind experience, those with poor self rated family economic status, those from other family structures, those classified as overweight and obesity, and those with sleep disorders, frequent consumption of sugar sweetened beverages, frequent consumption of takeout/delivery food, smoking, alcohol consumption, and low to moderate physical activity levels exhibited significantly higher risks across psychological sub health or emotional problems,conduct problems, and social adaptation difficulty ( OR =1.25-4.79, all P <0.05). Conclusions The psychological sub health condition of secondary vocational school students should not be neglected. Psychological sub health of secondary vocational school students is related to multiple factors such as demographic characteristics and lifestyle behaviors. Multi dimensional intervention measures should be implemented to improve their mental health.

ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.