AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

Kidney stones are a typical model of pathological mineralization, and the association between local mineralization imbalance and systemic ectopic calcification is complex. This review systematically summarizes three major advances in the field. Firstly, at the molecular level, inflammatory/immune modulation(Th-cell activation), metabolic dysregulation(aberrant calcium-phosphate/lipid metabolism), and epigenetic control(lncRNA-driven osteogenic differentiation)act in concert to drive Randall's plaque formation. Secondly, at the systemic level, nephrolithiasis shares the Klotho pathway with vascular calcification and bone-metabolic disorders, converging on the inhibition of Wnt/β-catenin and related axes, underscoring the global impact of calcium-phosphate homeostatic disruption. Thirdly, in translational medicine, GeoBioMed technologies dissect mineral heterogeneity, AI models predict recurrence risk(AUC=0.87), CRISPR-based interventions [silencing of metastasisassociated lung adenocarcinoma transcript 1(MALAT1)], and biomimetic materials(carbonate-apatite coatings)exhibit significant therapeutic promise. Future efforts should integrate single-cell multi-omics, microbiome modulation, and cross-organ dynamic monitoring to shift the therapeutic paradigm from stone removal to the precise restoration of mineralization homeostasis.

Objective To investigate the protective effects and potential mechanisms of the preparation of Abelmoschus manihot(L.)Medik(Jiahua Tablet)against acute radiation-induced myocardial injury,based on myo-cardial injury markers(sST2,cTnI)and oxidative stress damage-related indicators(SOD,MDA),and to provide new avenues for the prevention and treatment of radiation-induced heart disease(RIHD).Methods Sixty-nine patients with thoracic malignant tumor who received radiotherapy at the department of radiation oncology in Hospital Affiliated to Nanjing University of Chinese Medicine from December 2023 to November 2024 were enrolled in the study.Participants were randomly divided into control group(n=38)and observation group(n=31).The control group received standard radiotherapy in conjunction with conventional medications for RIHD,while the observation group was additionally administered Jiahua Tablet alongside the same regimen.Both groups took medications continuously for 1 month.Changes in serum levels of sST2,cTnI,SOD,and MDA were compared between the two groups 3 days prior to radiotherapy and 7 days after radiological therapy.Results On day 7 post-radiotherapy,the levels of sST2 and cTnI in the control group were highly elevated,showing statistically significant difference(P<0.01).In contrast,the levels of sST2 and cTnI in the observation group showed only mild elevation,and no statistically significant difference was observed(P>0.05).Between-group analysis demonstrated that post-treatment sST2 and cTnI levels in the observation group were substantially lower compared to those in the control group,indicating statistically significant difference(P<0.05).After treatment,SOD level in the control group was considerably lower compared to its pre-treatment level,and marked statistical significance was observed(P<0.01).SOD level in the observation group demonstrated a downward trend compared to baseline value,indicating no statistical significance(P>0.05).Between-group analysis demonstrated that post-treatment SOD level in the observation group was substantially elevated compared to that in the control group,indicating a highly significant disparity(P<0.05).After treatment,MDA level in the control group was considerably higher compared to its pre-treatment level,and a marked statistical significance was observed(P<0.05),whereas MDA level in the observation group showed only a mild increase compared to baseline value,with no statistically significant difference(P>0.05).Between-group analysis demonstrated that post-treatment MDA level in the observation group was substantially lower compared to that in the control group,demonstrating a remarkably statistically significant difference(P<0.01).Conclusion The preparation of Abelmoschus manihot(L.)Medik(Jiahua Tablet)effectively inhibits acute radiation-induced myocardial injury,with its potential mechanism closely linked to the suppression of oxidative stress responses.

Objective To investigate the protective effects and potential mechanisms of the preparation of Abelmoschus manihot(L.)Medik(Jiahua Tablet)against acute radiation-induced myocardial injury,based on myo-cardial injury markers(sST2,cTnI)and oxidative stress damage-related indicators(SOD,MDA),and to provide new avenues for the prevention and treatment of radiation-induced heart disease(RIHD).Methods Sixty-nine patients with thoracic malignant tumor who received radiotherapy at the department of radiation oncology in Hospital Affiliated to Nanjing University of Chinese Medicine from December 2023 to November 2024 were enrolled in the study.Participants were randomly divided into control group(n=38)and observation group(n=31).The control group received standard radiotherapy in conjunction with conventional medications for RIHD,while the observation group was additionally administered Jiahua Tablet alongside the same regimen.Both groups took medications continuously for 1 month.Changes in serum levels of sST2,cTnI,SOD,and MDA were compared between the two groups 3 days prior to radiotherapy and 7 days after radiological therapy.Results On day 7 post-radiotherapy,the levels of sST2 and cTnI in the control group were highly elevated,showing statistically significant difference(P<0.01).In contrast,the levels of sST2 and cTnI in the observation group showed only mild elevation,and no statistically significant difference was observed(P>0.05).Between-group analysis demonstrated that post-treatment sST2 and cTnI levels in the observation group were substantially lower compared to those in the control group,indicating statistically significant difference(P<0.05).After treatment,SOD level in the control group was considerably lower compared to its pre-treatment level,and marked statistical significance was observed(P<0.01).SOD level in the observation group demonstrated a downward trend compared to baseline value,indicating no statistical significance(P>0.05).Between-group analysis demonstrated that post-treatment SOD level in the observation group was substantially elevated compared to that in the control group,indicating a highly significant disparity(P<0.05).After treatment,MDA level in the control group was considerably higher compared to its pre-treatment level,and a marked statistical significance was observed(P<0.05),whereas MDA level in the observation group showed only a mild increase compared to baseline value,with no statistically significant difference(P>0.05).Between-group analysis demonstrated that post-treatment MDA level in the observation group was substantially lower compared to that in the control group,demonstrating a remarkably statistically significant difference(P<0.01).Conclusion The preparation of Abelmoschus manihot(L.)Medik(Jiahua Tablet)effectively inhibits acute radiation-induced myocardial injury,with its potential mechanism closely linked to the suppression of oxidative stress responses.

Objective To investigate the impacts of intervertebral foramen endoscopic surgery combined with silver needle hyperthermia therapy on lumbar spine function and local tenderness in patients with lumbar disc herniation(LDH).Methods From April 2020 to March 2023,100 LDH patients were randomly devided into a control group(50 cases)and an observation group(50 cases)through random number table method.The control group was treated with intervertebral foramen endoscopic surgery combined with conventional lumbar and dorsal muscle training,while observed group was treated with intervertebral foramen endoscopic surgery combined with silver needle warm therapy.The lumbar function,local tenderness,laboratory indicators,and adverse reactions were compared.Results The Japanese Orthopaedic Association(JOA)score increased in both groups after treatment,and observed group had obviously higher scores,the differences were statistically significant(P<0.05);After treatment,both groups showed a decrease in pain visual analogue scale(VAS)score,and observed group had obviously lower scores,the differences were statistically significant(P<0.05);The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),prostaglandin E2(PGE2),and 5-hydroxytryptamine(5-HT)in both groups decreased after treatment,and the observed group showed a more obvious decrease in all indicators,the differences were statistically significant(P<0.05);The incidence of adverse reactions was 4.00%(2/50)in observed group and 20.00%(10/50)in the control group,adverse reactions in observed group were obviously fewer,the difference was statistically significant(P<0.05).Conclusion The combination of intervertebral foramen endoscopic surgery and silver needle hyperthermia therapy can effectively improve lumbar spine function and alleviate local tenderness symptoms in patients with LDH.It is worthy clinical application.

Objective To characterize working memory performance in patients with chronic fatigue syndrome(CFS)and spleen-deficiency syndrome and to examine its associations with clinical symptoms by Sternberg working memory task(SWMT).Methods 31 CFS patients meeting both CDC-1994 criteria and consensus criteria for spleen-deficiency pattern were recruited from outpatient clinics and universities from September 2022 and June 2025.31 healthy controls were also recruited based on age,sex,and education.All subjects completed the SWMT.Group differences were analyzed.Within the CFS cohort,reaction time(RT)was correlated with scores on the checklist individual strength(CIS),36-item short-form health survey(sf-36),and fatigue scale-14(FS-14).Mediation was examined.Results RT lengthened with increasing memory load in both groups.CFS patients displayed slower RTs than controls in the baseline and 6-digit set(P<0.05).The 3-digit RT difference,though not significant(P>0.05),yielded a medium effect size(r=0.36).Accuracy did not differ between two groups.Among CFS patients,3-digit RT correlated positively with CIS total and the 4 sub-scale scores.6-digit RT correlated with the SF-36 health-transition dimension(r=0.396,P=0.027).CIS and FS-14 scores directly impaired SF-36 social functioning without working-memory mediating.Conclusion CFS patients with spleen-deficiency exhibit slowed processing speed rather than capacity loss.The close link between working-memory slowing and fatigue suggests a distinct neural basis.These results support the traditional concept"the spleen stores Yi"and integrate TCM pattern differentiation with modern cognitive neuroscience in CFS.

Objective To explore their inter-relationship,cognitive performance and cardio-electroencephalographic coupling in coronary heart disease(CHD)patients with heart-qi deficiency pattern were characterized.Methods Thirty CHD patients who met the diagnostic criteria for heart-qi deficiency were enrolled.Thirty healthy volunteers without heart-qi deficiency or CHD served as controls.Cognitive function was assessed with the repeatable battery for the assessment of neuropsychological status(RBANS).Simultaneous resting-state electrocardiogram and electroencephalogram were recorded,and the strength of heart-brain coupling was quantified by calculating the maximal information coefficient(MIC)between heart-rate variability(HRV)and EEG signals.Results Compared with controls,heart-qi deficiency CHD patients showed lower RBANS total scores and reduced performance in immediate memory,visuospatial/constructional ability,and attention.Significant between-group differences in HRV-EEG MIC values were observed at several channels(P<0.05).In patients,the MIC values for HRV-Beta(channel FC1)and HRV-Delta(channel F2)were positively correlated with RBANS total score(P<0.05).Conclusion CHD patients with heart-qi deficiency exhibit impaired cognition and altered cardio-electroencephalographic coupling.These findings suggest that heart-brain interactions may contribute to the pathophysiological mechanisms underlying cognitive decline in this population.

Objective To investigate the impacts of midazolam(MDZ)on the proliferation,migration,and invasion of esophageal cancer(EC)cells by regulating the monocyte chemotactic protein-1(CCL2)-C-C chemokine receptor 2(CCR2)signaling pathway.Methods QRT-PCR method was applied to determine the expression of CCL2 and CCR2 mRNA in EC tissue,adjacent cancer tissue,human normal esophageal epithelial cell HEEC,and EC cell Eca-109.MTT assay and colony formation were applied to measure cell proliferation.Scratch test,Transwell test,and TUNEL method were applied to determine cell migration,invasion,and apoptosis,respectively.The expression of CCL2-CCR2 signaling pathway proteins was determined using Western blot method.Results Compared with adjacent cancer tissues and normal human esophageal epithelial cells(HEEC),the mRNA and protein expression levels of CCL2 and CCR2 in cancer tissues and Eca-109 cells were increased(P＜0.05).Compared with the control group,the OD450 value,colony formation number,scratch healing rate,and invasive cell count of Eca-109 cells in the MDZ-L group,MDZ-M group,and MDZ-H group decreased,while the proportion of TUNEL positive cells increased(P＜0.05).Compared with the MDZ-H group,the OD450 value,colony formation number,scratch healing rate,and number of invasive cells in the MDZ-H+GW0742 group all increased,while the proportion of TUNEL positive cells decreased(P＜0.05).Compared with the control group,protein and mRNA expressions of CCL2 and CCR2 proteins in Eca-109 cells in the MDZ-L group,MDZ-M group,and MDZ-H group decreased(P＜0.05).Compared with the MDZ-H group,the MDZ-H+GW0742 group showed an increase in the expression of CCL2 and CCR2 proteins in Eca-109 cells(P＜0.05).Conclusion MDZ can inhibit the proliferation,migration,and invasion of EC cells by inhibiting the activation of the CCL2-CCR2 signaling pathway.