Diabetic retinopathy(DR)has emerged as the leading cause of vision loss among working-age people in many countries under the increasing prevalence of diabetes and the longevity of the population. The pathogenesis of DR is complicated and has not been fully elucidated at present, while the treatment methods of DR have not been greatly improved, mainly retinal laser photocoagulation, anti-vascular endothelial growth factor(VEGF)treatment and vitrectomy surgery. The current treatment methods not only have shortcomings, but also bring serious economic burden to patients. Therefore, new methods are needed to explore the pathogenesis of DR, discover new treatments or improve current treatments, and improve the satisfaction of DR patients. In recent years, the identification and quantification of proteins expressed in blood, retina, vitreous humor, aqueous humor, and tears of all observable DR patients and DR rats and differentially expressed proteins after drug intervention have provided new ideas for further exploring the pathogenesis, diagnosis and treatment of DR with the rise of proteomics, which put forward new insights into early detection and treatment.The proteomics of DR in recent years are reviewed, in order to provide new ideas for the diagnosis and treatment of DR.

Diabetic retinopathy(DR)has emerged as the leading cause of vision loss among working-age people in many countries under the increasing prevalence of diabetes and the longevity of the population. The pathogenesis of DR is complicated and has not been fully elucidated at present, while the treatment methods of DR have not been greatly improved, mainly retinal laser photocoagulation, anti-vascular endothelial growth factor(VEGF)treatment and vitrectomy surgery. The current treatment methods not only have shortcomings, but also bring serious economic burden to patients. Therefore, new methods are needed to explore the pathogenesis of DR, discover new treatments or improve current treatments, and improve the satisfaction of DR patients. In recent years, the identification and quantification of proteins expressed in blood, retina, vitreous humor, aqueous humor, and tears of all observable DR patients and DR rats and differentially expressed proteins after drug intervention have provided new ideas for further exploring the pathogenesis, diagnosis and treatment of DR with the rise of proteomics, which put forward new insights into early detection and treatment.The proteomics of DR in recent years are reviewed, in order to provide new ideas for the diagnosis and treatment of DR.

ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Shenxiong Huanglian Jiedu decoction on the clearance of amyloid β-protein （Aβ） and neuronal damage in the mouse model of Alzheimer's disease （AD）. MethodsA total of 36 SPF-grade 2-month-old C57BL/6J mice were used in this study， and the modeling was performed by bilateral hippocampal injection of Aβ oligomers in C57BL/6J mice. The experiment was conducted with a blank group， a sham operation group， a model group， low- and high-dose （3.27，6.54 g·kg^-1， respectively） Shenxiong Huanglian Jiedu decoction groups， and a positive control （donepezil hydrochloride， 0.65 mg·kg^-1） group. At the end of the drug intervention， the learning and memory abilities and the activities of mice were evaluated by the Morris water maze and open field tests. Brain histopathology was examined by hematoxylin-eosin and Nissl staining. Additionally， in vivo imaging was employed to measure the metabolism of fluorescent Aβ in the cerebrospinal fluid， and staining of ionized calcium-binding adapter molecule-1 （Iba-1） was employed to assess microglial activation in the hippocampal tissue. Additionally， neurotrophin-3 （NT-3） and brain-derived neurotrophic factor （BDNF） levels in the brain tissue and serum were determined by the immunofluorescence assay and enzyme-linked immunosorbent assay. Western blot was conducted to determine the expression of inflammation and pathway-related proteins in the hippocampal tissue. ResultsCompared with the blank group and the sham operation group， the escape latency of the mice in the model group was prolonged， the platform residence time was shortened， the hippocampal tissue showed pathological manifestations such as neuronal pyknosis， Nissl body dissolution， and microglia activation. The metabolic rate of fluorescent Aβ through cerebrospinal fluid was slowed down， and the expression levels of BDNF， NT-3， and interleukin-10 （IL-10） in the hippocampus were significantly decreased （P<0.01）. The expression levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88） and phosphorylated nuclear transcription factor-κB （p-NF-κB p65） in hippocampus were significantly increased （P<0.05， P<0.01）. Compared with the model group， the escape latency of mice in the low and high dose groups of Chinese medicine and donepezil group was shortened， and the platform residence time was prolonged. Neuronal karyopyknosis， Nissl body dissolution and microglia activation in hippocampus were improved. Fluorescence Aβ was metabolized faster by cerebrospinal fluid. The expression of BDNF and NT-3 in hippocampus was increased （P<0.01）， and the expression of TLR4， MyD88 and p-NF-κB p65 was significantly decreased （P<0.05， P<0.01）. The expression of TNF-α in the hippocampus of the high-dose group was significantly decreased （P<0.05）， and the expression of IL-10 was significantly increased （P<0.05）. The expression of TNF-α， IL-6 and IL-1β in the hippocampus of the donepezil group was significantly decreased （P<0.05， P<0.01）. ConclusionShenxiong Huanglian Jiedu decoction may mitigate neuronal damage and enhance cerebrospinal fluid flow in the mouse model of AD， thereby promoting the clearance of Aβ and improving the learning and memory abilities. These beneficial effects are likely mediated through the inhibition of microglial activation， reduction of inflammation， and modulation of the TLR4/MyD88/NF-κB signaling pathway.

Objective To explore the difference of efficacy and safety between denosumab and zoledronic acid in the treatment of patients with postmenopausal osteoporosis (PMOP), and to optimize the medication regimen for PMOP patients. Methods A total of 123 PMOP patients with high risk of fracture at the Second Affiliated Hospital of Naval Medical University from September 2021 to March 2024 were selected and randomly divided into two groups: the denosumab group (n=63) and the zoledronic acid group (n=60). Both groups underwent one-year treatment and follow-up, bone metabolism indexes, lumbar vertebrae, femoral neck, and total hip bone mineral density (BMD) were monitored, and any adverse reactions were documented. Results After treatment, the lumbar vertebrae and total hip BMD of patients in the denosumab group and the zoledronic acid group were significantly improved (P＜0.05); the femoral neck BMD of patients in the zoledronic acid group was also significantly improved (P＜0.05). The improvement of lumbar vertebrae BMD in the denosumab group was significantly better than that in the zoledronic acid group, while the improvement of femoral neck and total hip BMD in the zoledronic acid group was significantly better than that in the denosumab group (P＜0.05). Bone metabolism indicators were significantly improved in both groups (P＜0.05), and no significant liver and kidney dysfunction were observed. A total of 7 patients in the zoledronic acid group had mild adverse reactions and 5 patients in the denosumab group had mild adverse reactions. Conclusions Denosumab significantly increased lumbar vertebrae BMD and improved bone metabolism markers in PMOP patients, thus reducing risk of fracture and demonstrating good safety.

ObjectiveTo understand the development stages and use of policy tools of general practitioner policies in China since it was first proposed, to summarize the experience and explore the shortcomings, so as to provide references for the adjustment and optimization of China’s general practitioner policies. MethodsContent analysis and mathematical statistics analysis were used to conduct a quantitative research on 111 policy documents with 422 policy items involving general practitioners at the national level from 1997 to 2023, through a three-dimensional analysis framework integrating policy tools, human capital process and policy development stages. ResultsCapacity‑building policy tools were most frequently used in general practitioner policies, and the policy tools gradually shifted from mandate to inducement. The general practitioner policies paid less attention to the career selection link, but paid full attention to every segment of human capital links, with a comprehensive application of policy tools observed in the integrated development stage, despite the existence of unbalanced internal distribution. ConclusionIt is suggested to promote the use of incentive policy tools and to explore multiple approaches based on incentive theory; pay attention to the career selection link for guiding the employment of general practitioners; take the appropriateness between the policy tools and human capital process into comprehensive consideration, striking a dynamic balance of the internal structure of general practitioner policies.

ObjectiveTo analyze the characteristics of policy texts related to the physician periodic assessment system in China, providing references for the improvement of the system. MethodsContent analysis was employed, examining 116 policy documents from three dimensions: policy process, policy themes, and policy tools. ResultsA total of 298 codes were obtained. The number of policies related to the periodic assessment of physicians showed an overall trend of increasing first and then decreasing, with the peak annual issuance period between 2011 and 2021, and the average number of policy texts showing a downward trend. Policy documents were summarized into 3 levels: physician periodic assessment work, individual behavior, and institutional systems, encompassing a total of 8 categories of themes. The proportion of supply-oriented, environmental-oriented, and demand-oriented policy tools were 4.03%, 60.40%, and 35.57%, respectively. Moreover, environmental-oriented tools continued to dominate over time, followed by demand-oriented tools, with supply-oriented tools being the least. ConclusionThe policy themes are relatively broad and difficult to implement, focusing on establishing regulations while neglecting resource provision, and failing to continuously improve the construction of the system. It is recommended to clearly define the scope of the periodic assessment management, improve supporting systems, increase resource supply, and continuously promote the execution of assessments and policy revisions.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

[Objective] To establish a method for detecting the potency of recombinant human coagulation factor Ⅶa for injection. [Methods] By adding the sample and factor Ⅶ deficient plasma to the sample cup and activating the reaction with prothrombin time assay reagent (PT reagent), the coagulation time of the sample was determined by the change in magnetic bead swing amplitude in the sample cup. The logarithm of coagulation time was inversely proportional to the logarithm of human factor Ⅶa potency. [Results] Under the experimental conditions, the specificity of the methodology was evaluated through spiked recovery, and the recovery rates ranged from 90.0% to 110.0%. Within the range from 0.125 to 1.000 IU/mL, there was a good linear response between the potency and coagulation time of the standard and sample, with correlation coefficients r>0.99. As for the accuracy and repeatability, the recovery rates of various concentrations detected in the stock solution were 101.0%, 100.0% and 112.0%, respectively, with RSD values of 2.6%, 4.0% and 0.0%, respectively. The recovery rates of various concentrations in finished product testing were 104.0%, 94.7% and 112.0%, respectively, with RSD values of 1.9%, 2.4% and 0.0%, respectively. As for the intermediate precision, the RSD were 4.5% and 3.7%, respectively. After treated with sample diluent, the sample was tested at room temperature for 6 hours and still exhibited relatively stable biological activity. [Conclusion] This detection method is accurate, stable, easy to operate and highly automated, and is suitable for detecting the potency of recombinant human coagulation factor Ⅶa for Injection.