ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective:To analyze the current allocation situation and equity of Class B large medical equipment in China,and provide references for reasonably optimizing the allocation of medical equipment.Methods:Based on the allocation data of Class B large medical equipment in China at the end of the 13th Five Year Plan period,the agglomeration degree method was used to evaluate the equity of equipment allocation in various regions from the dimensions of geography,population,and economic development.Results:The current allocation of Class B large medical equipment per million population was 3.19,and the eastern region(3.64)was higher than the central region(3.42),the central region(2.24)was higher than the western region.The agglomeration degree of medical equipment based on geographical area showed that most of the equipment in the eastern region was in a rich state,and the allocation equity was relatively good in the central region,but generally poor in the western region.The agglomeration degree of medical equipment based on population distribution was higher in the eastern region than in the central region and even higher in the western region.The equipment in the eastern region could basically meet the demand of the local population,while the allocation in the central and western regions was slightly insufficient.The distribution of medical equipment agglomeration degree based on economic development varied significantly among different regions,and the allocation equity of central region was generally better than that of eastern and western regions.Conclusion:The total allocation of Class B large medical equipment in China is not high,and the government needs to continue planning and improving it.The distribution of medical equipment allocation based on geography,population and economic development is unbalanced among the eastern,central and western regions.Improving the equity of medical equipment allocation also needs to consider regional differences and characteristics according to local conditions.

Objective To study the diffusion mode and characteristics of large medical equipment allocation and use management policies among different institutions or regions,so as to provide reference for the improvement of policies.Methods The policies on the allocation and use management of large medical equipment released from Janu-ary 1994 to December 2022 were searched on the official websites of the central government,local governments,and health commissions,and databases such as"Peking University Magic".Based on the theory of policy diffu-sion,It analyzed the diffusion characteristics,diffusion mode and influencing factors of large medical equipment allo-cation and use management policy in combination with factors such as policy diffusion intensity,diffusion width,dif-fusion speed,and diffusion direction,and through the policy network analysis identified interrelationships between policies across agencies or across regions.Results It included 161 policy documents for analysis,including 25 central policies and 136 local policies.The development of large medical equipment allocation and use management policies in China can be divided into four periods.The policies with high diffusion intensity,breadth and fast diffusion speed were mainly policy documents such as large medical equipment allocation plan and management measures issued by the National Health Commission,and at the same time,the"top-down"policy vertical diffusion modelwas the main one.Conclusion There were differences in the diffusion effects of large medical equipment allocation and use management policies at different stages,and the policy diffusion effect was obvious in the innovation and develop-ment period.It found that policy diffusion was affected by factors such as the division of administrative powers and responsibilities,and policy types.

Objective To investigate the impact of acacetin(Aca)on angiogenesis in diabetes retinopathy(DR)rats by regulating Hippo signaling pathway.Methods Sixty SD rats were grouped into the control group,the DR group,the Aca low dose group(10 mg/kg),the Aca medium dose group(20 mg/kg),the Aca high dose group(30 mg/kg)and Hippo-YAP signaling pathway inhibitor Verteporfin group(Aca high dose 30 mg/kg+Verteporfin 0.8 pmol/kg),with 10 rats in each group.Except the control group,streptozotocin and high-fat feed were used to construct the DR model.Body weight and fasting blood glucose(FBG)levels of rats were measured.Fluorescein angiography(FFA)was applied to observe retinal angiogenesis and fluorescein leakage.Enzyme linked immunosorbent assay was applied to detect serum levels of vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2).Pathological changes of retinal tissue were observed by hematoxylin-eosin staining.Western blot assay was applied to detect expression levels of VEGF,hypoxia-inducible factor 1 alpha(HIF-1α),vascular cell adhesion molecule-1(VCAM-1)and Hippo signaling pathway proteins.Results Compared with the control group,retinal cells of rats in the DR group were arranged in a disordered and loose manner,with neovascularization and a large amount of fluorescein leakage,and body weight,the expression of large tumor suppressor homolog 2(LATS2),p-Yes-associated protein(YAP)were reduced.FBG and expression levels of VEGF,Ang-2,HIF-1α,VCAM-1,YAP,transcription activator with PDZ binding motif(TAZ),TEA domain family member 1(TEAD1)were increased(P＜0.05).Compared with the DR group,retina cells of rats in the Aca low,medium and high-dose groups and the Verteporfin group were arranged neatly,with reduced neovascularization and fluorescence leakage,body weight and the expression levels of LATS2 and p-YAP were increased,and FBG,expression levels of VEGF,Ang-2,HIF-1α,VCAM-1,YAP,TAZ and TEAD1 were reduced(P＜0.05).The effect was more obvious in the Aca high dose group.However,there was no significant difference in each indicator between the Verteporfin group and the Aca high dose group.Conclusion Aca can inhibit angiogenesis and improve retinal pathological damage in DR rats,and its mechanism of action may be related to regulating the Hippo signaling pathway.

Objective To study Chinese medicine consultation strategies to achieve rapid capture of key information about patients'conditions and to advance the development of objectification in Chinese medicine consultation.Methods A symptom questioning model based on frequent pattern mining algorithm in correlation analysis was used,and a cross-merging method was used to establish a TCM symptom questioning strategy between single-system symptom questioning and multi-system integrated symptom questioning in TCM,to achieve the shortest time and highest efficiency in capturing key information about the patient's condition.Results A breakthrough from single-system questioning to five-system integrated questioning was achieved,and the process of efficiently obtaining information about the patient's condition was achieved through both single-system and five-system symptom questioning modes,and the system was able to obtain 92%of the patient's symptom information with at most 65%fewer questions than the traditional scale questioning method,greatly improving the efficiency of obtaining information about the patient's symptoms.Conclusion With the two different symptom questioning modes,the traditional TCM questioning mode of asking patients based on scales is broken,the time to obtain symptoms from patients is shortened,the questioning process is simplified,and discrepancies due to inexperience or human subjectivity are reduced,which can be used in clinical aids to diagnosis in TCM.

Objective:To investigate the CT imaging features of fat-poor primary retroperitoneal liposarcoma ( PRPLS).Methods:The CT signs of 43 fat-poor PRPLS cases among 128 PRPLS patients confirmed by pathology, including multiple nodules composing or multiple nodules fusing, tumor heterogeneity, were retrospectively evaluated.Results:Of 43 fat-poor PRPLS cases, 28 cases(65%) showed multiple nodules composing or multiple nodules fusing on CT images, 15 cases (35%)demonstrated single mass. Seventeen cases showed tumor heterogeneity on pre-contrast scan, 18 cases showed tumor heterogeneity on contrast scan, 13 cases showed tumor heterogeneity on both pre-contrast and contrast scan, 22 cases (51%)showed tumor heterogeneity on pre-contrast or contrast scan.Conclusion:CT signs of multiple nodules composing or multiple nodules fusing, especially tumor heterogeneity may help establishing diagnosis of fat-poor PRPLS.

Malaria is a significant global infectious disease that once wreaked havoc in China as well. In recent years, the global malaria control situation has stagnated, and China is also facing a huge threat of imported malaria. So, effective malaria vaccines are urgently needed as a supplementary strategy to the existing prevention and control measures. Compared to vaccines targeting the erythrocytic stage and those designed to block transmission, vaccines aimed at preventing infection during the pre-erythrocytic stage have attracted more attention and have made a series of progress in recent years. At present, the only two malaria vaccines recommended by the World Health Organization (WHO) are pre-erythrocytic vaccines. In this paper, the current situation and trend of pre-erythrocytic malaria vaccine research and development are reviewed, intending to provide a reference for the research, development, and application of malaria vaccines in the future.

Objective To investigate the shedding of CAV2-ΔE3-CGS after immunization and the background of canine adenovirus (CAV) infection, and to establish a dual fluorescent quantitative PCR detection method for rabies virus (RV) and canine adenovirus type 2 (CAV2). Methods A dual fluorescent quantitative PCR detection method was established by designing specific primers and probes for E1 gene of CAV and G gene of RV for the detection of CAV2-ΔE3-CGS. Oral swabs, anal swabs and environmental samples of stray dogs from experimental animal farm and dog detention center were tested. Results The standard curves generated by this method were Y=-3.351 × logX + 44.895, R² = .999 and Y=-3.413 × logX + 45.192, R²=0.996, respectively. The linear relationships were good, and the minimum detection limits were both 102 copies/μL. CAV2-ΔE3-CGS was not detected in experimental animal farm. CAV was detected in dog detention center, and the positive rates were 5.88% (5/85) in oral swabs, 8.24% (7/85) in anal swabs, and 4% (1/25) in environmental samples. Conclusion The dual fluorescent quantitative PCR method can be used for the detection of CAV2-ΔE3-CGS after immunization and the investigation of CAV infection. The present study has shown that no CAV2-ΔE3-CGS has been detected after immunization and CAV infection rate of stay dogs is low in Shanghai. CAV2-ΔE3-CGS oral immunization meets requirement and is applicable.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).