ObjectiveTo evaluate the clinical efficacy and safety of Qidan Tangshen Granules （芪丹糖肾颗粒， QTG） in the treatment of early diabetic kidney disease （DKD） with qi deficiency， blood stasis， and kidney deficiency syndrome， and to explore its mechanism. MethodsA double-blind， double-simulated method was used to enroll 200 patients with early DKD and qi deficiency， blood stasis， and kidney deficiency syndrome. Patients were randomly assigned in a 1∶1 ratio to the treatment group （100 cases） and the control group （100 cases）. The treatment group received QTG plus a valsartan capsule simulant， while the control group received valsartan capsules plus a QTG simulant， both for 12 weeks. The primary outcome was the urinary albumin-to-creatinine ratio （UACR）. Secondary outcomes included estimated glomerular filtration rate （eGFR）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （PBG）， glycated hemoglobin （HbA1c）， and traditional Chinese medicine （TCM） syndrome scores （including individual symptom scores for fatigue， dull complexion， soreness and weakness of the waist and knees， headache and chest pain， irritability， spontaneous sweating， thirst and polydipsia， polyphagia， polyuria， numbness of the limbs， and the total TCM syndrome score）. Oxidative stress markers including serum 8-hydroxy-2'-deoxyguanosine （8-OHDG）， 3-nitrotyrosine （3-NT）， and superoxide dismutase （SOD） were also assessed. Clinical efficacy and TCM syndrome efficacy were evaluated after treatment， and routine blood tests， urinalysis， and liver function tests were conducted and adverse reaction during the tria was recorded to assess safety. ResultsA total of 191 patients completed the study （95 in the treatment group and 96 in the control group）. The treatment group showed significant reductions in UACR， FBG， PBG， and HbA1c levels after treatment （P＜0.05 or P＜0.01）. The single TCM symptom scores except for polyphagia and total TCM syndrome scores significantly decreased （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had signi-ficantly lower UACR， FBG， PBG levels， and total TCM syndrome scores， sinlge symptoms scores except for polyphagia and limb numbness （P＜0.05 or P＜0.01）. Among 40 randomly selected patients （21 cases in the treatment group and 19 cases in the control group） for oxidative stress analysis， there were no significant differences in SOD， 3-NT， and 8-OHDG levels before and after treatment within or between groups （P＞0.05）. The overall effective rate in the treatment group was 64.2% （61/95） and 39.6% （38/96） in the control group， while the TCM syndrome efficacy rates were 80.0% （76/95） and 24.0% （23/96）， respectively， with the treatment group showing superior efficacy （P＜0.01）. No significant differences were observed in routine blood tests， urinalysis， or liver function indices before and after treatment in either group （P＞0.05）. The incidence of adverse reactions was 8.4% （8/95） in the treatment group and 9.4% （9/96） in the control group， with no statistically significant difference （P＞0.05）. ConclusionQTG can effectively reduce UACR and blood glucose levels， alleviate clinical symptoms， and improve clinical efficacy in patients with early DKD with qi deficiency， blood stasis， and kidney deficiency syndrome. The treatment is well-tolerated and safe， with no significant impact on oxidative stress markers.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective:To explore the effectiveness of 18F-deuterated-Florbetapir (D3FSP) PET/CT imaging in detecting β-amyloid (Aβ) deposition in the brain and its correlation with plasma biomarkers. Methods:A retrospective analysis was conducted on 79 patients (32 males, 47 females; age(66±7)years) who underwent 18F-D3FSP PET/CT imaging from June 2022 to November 2023 at the First Affiliated Hospital, Guangzhou Medical University, as a part of the Greater Bay Area Healthy Aging Brain Longitudinal Cohort Study (GHABS). Based on the Alzheimer′s Disease Neuroimaging Initiative cohort standard protocol, patients were categorized into cognitively unimpaired (CU) group, mild cognitive impairment (MCI) group, and Alzheimer′s disease (AD) group. Brain regions were segmented using the AW workstation and the SUV ratio (SUVR) was calculated with the cerebellum as the reference region. One-way analysis of variance, Bonferroni correction and Pearson correlation analysis were used to analyze data. The ROC curve analysis was used to analyze the cut-off value and the diagnostic efficacy of SUVR. Results:There were 48, 15 and 16 cases in CU, MCI and AD groups respectively. During the transition from CU to MCI and then to AD, there was a rising trend in SUVR ( F values: 11.15-22.38, all P<0.001) across the whole brain and various brain regions (bilateral frontal lobes, bilateral anterior cingulate gyrus, bilateral precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes). SUVRs of the right anterior cingulate gyrus and bilateral precuneus were different between the CU and MCI groups (all P<0.017), and those of bilateral frontal lobes, right precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes were different between the MCI and AD groups (all P<0.017). SUVRs of brain regions were negatively correlated with cognitive scale scores ( r values: from -0.57 to -0.37, all P<0.001), and were positively correlated with plasma phosphorylated tau181 (p-tau181, r values: 0.50-0.61, all P<0.001). The ROC curve analysis suggested that the cut-off value of SUVR in the precuneus for distinguishing CU from AD was 1.20, with the AUC, sensitivity, specificity and accuracy of 0.85, 12/16, 91.7%(44/48)and 87.5%(56/64), respectively. Conclusion:18F-D3FSP PET/CT imaging has good clinical application value in assessing the deposition sites and the extent of Aβ in the brain, which is related to clinical cognition and plasma p-tau181 level.

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Objective : To investigate the effect of micro/nano hierarchical structures on the adhesion and proliferation of MC3T3-E1 cells, evaluate the drug delivery potential of titanium surfaces, and provide a reference for the modification of selected areas of titanium surfaces to enhance drug delivery and slow drug release. Methods : Pure titanium samples (10 mm in diameter and 2.5 mm in thickness) were randomly divided into a polished group (T), anodized group (TO), and micro/nano hierarchical structure group (FTO) according to the surface treatment of the titanium. The T group was polished, the TO group was treated with anodic oxidation technology, and the FTO group was treated by femtosecond laser etching combined with anodic oxidation technology. The three surface morphologies were observed by scanning electron microscopy (SEM), the wettability of the surface was measured by the contact angle, and the surface chemical composition was analyzed by X-ray energy dispersive spectroscopy (EDS). The depth of the FTO structure and the surface roughness were measured by confocal laser scanning microscopy (CLSM). MC3T3-E1 cell adhesion proliferation and differentiation on the surface of each group of samples was assessed by immunofluorescence staining, CCK-8, and semiquantitative analysis of Alizarin staining. A freeze-drying method was applied to load recombinant human bone morphogenetic protein-2 (rhBMP-2), and an enzyme-linked immunosorbent assay (ELISA) was used to assess the drug-loading potential of different surface structures. Results: SEM revealed that the surface of T group titanium plates showed uniform polishing marks in the same direction. The surface of the TO group was a nanoscale honeycomb-like titanium dioxide (TiO2) nanotube structure, and the FTO group formed a regular and ordered micro/nano layered structure. The contact angle of the FTO group was the smallest at 32° ± 1.7°. Its wettability was the best. The average depth of the first-level structure circular pores was 93.6 μm, and the roughness was 1.5-2 μm. The TO and FTO groups contained a high percentage of oxygen, suggesting TiO2 nanotube formation. The FTO group had the most significant surface cell proliferation (P<0.001) and the largest cell adhesion surface area (P<0.05). rhBMP-2 was slowly released for 14 d after loading in the FTO group and promoted extracellular matrix mineralization (P<0.001). Conclusion Titanium surface microprepared hierarchical structure has the effect of promoting MC3T3-E1 cell adhesion, proliferation, and osteogenic differentiation with drug loading potential, which is a new method of titanium surface treatment.

Objective:To investigate the pathogenesis, selection of endovascular treatment (EVT) strategies, and efficacies of acute vertebrobasilar artery occlusion (AVBAO) of different lesion sites.Methods:One hundred and five patients with AVBAO, admitted to and accepted EVT in our hospital from February 2017 to September 2019, were chosen in our study. The data of disease onset, imaging findings, EVT status, perioperative complications, and prognoses of these patients were collected. According to DSA results, the involved lesions were divided into 4 sites: the upper segment of basilar artery (BA), the middle segment of BA, the lower segment of BA, and the intracranial segment of vertebral artery (V4 segment), and patients with tandem lesions would be recorded as distal lesions. The risk factors, EVT strategies, and prognoses 90 d after follow-up (modified Rankin scale [mRS] scores≤3: good prognosis) were compared in patients with 4 different lesion sites.Results:There were significant differences in etiological classifications and percentage of patients combined with atrial fibrillation among patients with 4 different lesion sites ( P<0.05). There was significant difference in proportion of patients accepted emergency stent implantation among patients with 4 different lesion sites ( P<0.05): those with lesions at the V4 segment had the highest proportion of patients accepted emergency stent implantation (79.55%), followed by those with lesions at the lower segment of BA (50.00%). There was significant difference in EVT time (the time from arterial puncture to successful recanalization of occluded vessels) among patients with 4 different lesion sites ( P<0.05): the EVT time in patients with lesions at the middle segment of BA was the shortest (87.5 [58.5, 130.8] min), and the EVT time in patients with lesions at the lower segment of BA was the longest (115.0 [81.0, 163.0] min). There was no statistical difference among patients with different lesion sites in good prognosis rate 90 d after follow-up ( P>0.05). Conclusion:The pathogenesis of patients with different AVBAO lesion sites is different, so different EVT strategies should be adopted.

Objective:To compare the dosimetric difference between intensity-modulated photon radiaotherapy (IMRT) planning and intensity-modulated proton radiotherapy (IMPT) planning for glioma.Methods:The clinical data of 15 glioma patients who underwent IMRT in ion medical center of the First Affiliated Hospital of USTC from November 2020 to April 2022 were retrospectively analyzed. IMRT planning and IMPT planning were designed for the image of each patient in the therapy planning system. Main dosimetric parameters were compared including plan target volume (PTV), coverage index (CI), dose homogeneity index (HI), and maximal dose (D max) and mean dose (D mean) of organs at risk between both plans. Results:There were no significant differences between IMRT planning and IMPT planning in terms of D max and D mean of PTV1 and PTV2, CI and HI (all P > 0.05). Compared with IMRT planning, brainstem D mean [6.92 GyE (0.09 GyE, 12.58 GyE) vs. 24.41 GyE (2.59 GyE, 34.18 GyE)], left optic nerve D max [0.78 GyE (0.04 GyE, 25.18 GyE) vs. 20.42 GyE (6.38 GyE, 37.17 GyE)], left optic nerve D mean [0.10 GyE (0.01 GyE, 11.63 GyE) vs. 9.74 GyE (2.99 GyE, 20.87 GyE)], right optic nerve D mean [1.57 GyE (0.13 GyE, 14.90 GyE) vs. 14.08 GyE (2.66 GyE, 23.67 GyE)], left len D max [0 GyE (0 GyE, 2.91 GyE) vs. 4.84 GyE (1.42 GyE, 5.48 GyE)], left len D mean [0 GyE (0 GyE, 1.73 GyE) vs. 3.84 GyE (1.25 GyE, 4.30 GyE)], right len D max [0.25 GyE (0.04 GyE, 4.55 GyE) vs. 4.28 GyE (1.58 GyE, 5.84 GyE)], right len D mean [0.16 GyE (0.01 GyE, 1.95 GyE) vs. 3.73 GyE (1.04 GyE, 4.86 GyE)], pituitary D max [6.97 GyE (0.18 GyE, 39.70 GyE) vs. 36.60 GyE (2.74 GyE, 45.19 GyE)], pituitary D mean [1.36 GyE (0.06 GyE, 13.85 GyE) vs. 24.74 GyE (2.42 GyE, 32.80 GyE)], hippocampus D max [5.10 GyE (0.24 GyE, 26.52 GyE) vs. 35.83 GyE (5.03 GyE, 46.11 GyE)], hippocampus D mean [0.36 GyE (0.04 GyE, 25.65 GyE) vs. 18.79 GyE (2.37 GyE, 28.10 GyE)] in IMPT planning were lower, and the differences were statistically significant (all P < 0.05). There were no statistical differences in brainstem D max [51.98 GyE (0.66 GyE, 53.43 GyE) vs. 53.29 GyE (3.87 GyE, 53.48 GyE)], right optic nerve D max [9.60 GyE (0.01 GyE, 43.32 GyE) vs. 25.37 GyE (3.45 GyE, 41.25 GyE)] of both plans (all P > 0.05). Conclusion:In the radiotherapy for glioma, IMRT and IMPT can meet the dose demand in clinic. Furthermore, IMPT planning can protect organs at risk and reduce radiation dose in hippocampus, brainstem, optic nerve, lens and pituitary.

Objective:To investigate the surgical method and curative effect of resection of craniopharyngioma through sub-frontal longitudinal fissure duramater-keyhole approach.Methods:The clinical data, imaging data of 179 patients with craniopharyngioma treated by sub-frontal longitudinal fissure duramater-keyhole approach from January 2017 to January 2021 in Sanbo Brain Hospital Capital Medical University were studied retrospectively.Results:Through this approach, total resection in 175 cases (97.77%), near total resection in 2 cases (1.12%), partial resection in 2 cases (1.12%); drilling of the tuberculum sellae in 31 cases (17.32%); the pituitary stalk was reserved in166 cases (92.74%), preserved in 13cases (7.26%); papillary craniopharyngioma in 27 cases (15.08%), ameloblastic craniopharyngioma in 152cases (84.92%); postoperative visual acuity improved in 65 cases (36.31%), not improved in 53 cases (29.61%), decreased in 6 cases (3.35%); electrolyte disorder in 101 cases (56.42%), polydipsia and polyuria in 65cases (36.31%), cerebrospinal fluid rhinorrhea in 3 cases (1.68%), hydrocephalus in 6 cases (3.35%). Postoperative hematoma in 2 (1.12%) cases and cerebral infarction in 6 cases (3.35%), intracranial infection in 8 cases (4.47%), postoperative disturbance of consciousness in 4 cases (2.23%) and death in 3cases (1.68%).Conclusions:Sub-frontallongitudinal fissure duramater-keyhole approach is an effective combination of minimally invasive and delicate surgery principle. It is a safe and effective method for the treatment of craniopharyngioma.

Objective:To analyze the surgical (anatomical) approach of craniopharyngioma based on the concept of anterior central space of brain base.Methods:The clinical data of MRI images of 10 cases of craniopharyngioma who treated in Sanbo Brain Hospital, Capital Medical University from January 2021 to December 2021 were analyzed retrospectively. The brain cisterns involved in the growth of craniopharyngioma were analyzed from the perspective of anterior central space of brain base. Meanwhile, the surgical approach and the basis of selection were discussed.Results:Among all the surgical approaches that can reach the anterior central space of the brain base, the fronto-basal interhemispheric approach was the best.Conclusions:The concept of anterior central space of the brain base is a new observation and interpretation of the anatomy of the brain base from a new perspective, and then create a new concept of brain base surgery. As a new method to analyze the surgical anatomy of this area, its inclusion has important clinical significance.