BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

Objective To investigate the effects of Aconite decoction （AD） on the viability and polarization of murine RAW264.7 macrophages induced by lipopolysaccharide （LPS） or interleukin-4 （IL-4）. Methods Cytotoxicity of AD was assessed by the CCK-8 assay. RAW264.7 cells were polarized toward M1 phenotype by LPS or M2 phenotype by IL-4, followed by treatment with varying concentrations of AD. Macrophage polarization was analyzed by flow cytometry. Quantitative PCR was performed to measure mRNA expression of polarization-associated markers （IL-6, iNOS, Arg1, and Ym1）. ELISA was used to quantify secreted cytokines （TNF-α and IL-10）in the supernatant. Results At non-toxic concentrations, IL-6 and iNOS mRNA levels in LPS-stimulated cells were significantly upregulated while Arg1 and Ym1 expression in IL-4-treated groups were downregulated by AD. Concurrently, TNF-α secretion in LPS-induced M1 polarization was enhanced but IL-10 production in IL-4-induced M2 polarization was suppressed by AD. Conclusion AD could promote macrophage proliferation and viability, augments LPS-driven M1 polarization, and inhibit IL-4-mediated M2 polarization, which provided experimental evidence for the potential application of AD in tumor immunotherapy.

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Objective To analyze the expression of SPAG5 in gastric cancer tissues and its regulatory roles in gastric cancer cell growth.Methods TCGA analysis,immunohistochemistry,and immunofluorescence staining were used to analyze the expression patterns of SPAG5 and MKi67 in gastric cancer and adjacent tissues.In gastric cancer AGS and MGC803 cells,the effects of lentivirus-mediated SPAG5 knockdown on cell growth and apoptosis were evaluated using Celigo,MTT,clone formation assays and flow cytometry.Results Proteinatlas and TCGA database analysis suggested that SPAG5 was highly expressed in gastric cancer,and Kaplan-Meier analysis and GEPIA analysis showed high expressions of SPAG 5 in lung adenocarcinoma,breast cancer,hepatocellular carcinoma,pancreatic carcinoma,cervical cancer and bladder carcinoma.Immunohistochemistry revealed that SPAG5 was highly expressed in gastric cancer tissues(P<0.001),and immunofluorescence colocalization analysis demonstrated a significant correlation between SPAG5 and MKI67(R=0.393,P<0.001).RT-qPCR and Western blotting showed that SPAG5 was highly expressed in MKN74,BGC823,MGC803,SGC7901 and AGS cells.In AGS and MGC803 cells,SPAG5 knockdown significantly inhibited proliferation and promoted apoptosis.Conclusions The expressions of SPAG5 and MKi67 are correlated in gastric cancer tissues,and SPAG5 knockdown inhibits the proliferation of gastric cancer cells.SPAG5 is associated with the prognosis of gastric cancer patients and may serve as a promising biomarker for gastric cancer.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective To analyze the current research status and hotspot issues of performance assessment in tertia-ry public hospitals in China,providing reference for subsequent research and practice.Methods Using"performance assessment of tertiary public hospitals"as the main keyword,a total of 520 articles were retrieved from the CNKI ac-ademic journal database from January 30,2019,to January 30,2024.After further screening of literature based on the inclusion and exclusion criteria,a total of 364 eligible articles were obtained.Visual analysis was conducted using the VOSviewer tool.Results The number of publications increased annually from 2019 to 2021,with a decline ob-served in 2022-2023."Chinese Journal of Health"published the most articles on performance assessment in tertiary public hospitals.Research institutions mainly focused on universities,health administrative departments,and hospi-tals.The hotspot clusters of research included performance assessment,public hospitals,target management,high-quality development,tertiary hospitals,and operational efficiency.Conclusion Performance assessment in tertia-ry public hospitals has received widespread attention,with rich connotations and obvious guiding effects,but further research is needed to deepen and explore related topics.

The performance evaluation of tertiary public hospitals aims to strengthen functional positioning,and the weight of indicators such as the proportion of surgery is relatively high in the evaluation indicators.In this con-text,some tertiary comprehensive hospitals with a high proportion of internal medicine business are facing significant challenges in sustained development.It comprehensively reviews the impact of performance evaluation indicators on the direction of internal medicine specialties,and uses SWOT analysis tools to condense the sustainable develop-ment path of tertiary public hospitals.This includes growth strategies(improving the ability to treat difficult and criti-cal diseases,undertaking scientific and educational tasks),transformational strategies(technological innovation,price approval),multiple business strategies(adjusting outpatient and inpatient structures,building specialized disease centers,etc.),and defensive strategies(reasonable diagnosis and treatment,clinical pathways),inorder to provide reference for hospital managers.

Objective To analyze the problems existing in the homogenization management of multi-branch hospitals based on the annual performance assessment data,and provide reference for promoting the high-quality development of public hospital branch districts.Methods Based on the Performance Assessment Operation Manual of National Tertiary Public Hospitals(2022 edition),10 indicators including the proportion of discharged patients undergoing surgery and the proportion of fourth-level surgery were screened,and the functional positioning,quality and safety,revenue and expenditure structure,and cost control of 4 hospitals of a certain medical institution from 2022 to 2023 were descriptively analyzed.Results The CMI value and the proportion of discharged surgery in the main hospital were significantly better than those in the branch hospitals,and there was no significant difference in the medical quality indicators of the four hospitals,and the operation efficiency of the branch hospital with outstanding specialty characteristics was better than that of other hospitals.Conclusion Public hospitals pay more attention to the"big specialty,small comprehensive"mode in the layout of branch districts,pay more attention to the quality control management at the specialty level in medical quality management,and strengthen the benefit analysis of different hospitals in the same specialty in operation management.

Objective To analyze the current research status and hotspot issues of performance assessment in tertia-ry public hospitals in China,providing reference for subsequent research and practice.Methods Using"performance assessment of tertiary public hospitals"as the main keyword,a total of 520 articles were retrieved from the CNKI ac-ademic journal database from January 30,2019,to January 30,2024.After further screening of literature based on the inclusion and exclusion criteria,a total of 364 eligible articles were obtained.Visual analysis was conducted using the VOSviewer tool.Results The number of publications increased annually from 2019 to 2021,with a decline ob-served in 2022-2023."Chinese Journal of Health"published the most articles on performance assessment in tertiary public hospitals.Research institutions mainly focused on universities,health administrative departments,and hospi-tals.The hotspot clusters of research included performance assessment,public hospitals,target management,high-quality development,tertiary hospitals,and operational efficiency.Conclusion Performance assessment in tertia-ry public hospitals has received widespread attention,with rich connotations and obvious guiding effects,but further research is needed to deepen and explore related topics.