ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy （DR） and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D （NLRP3/Caspase-1/GSDMD） signaling pathway. MethodsHuman retinal microvascular endothelial cells （HRMEC） were divided into the blank group， model group， and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group， all groups were induced with 40 mmol·L^-1 high glucose， and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum， respectively， based on the induction. After 24 h of culture， the levels of interleukin （IL）-1β and IL-18 were measured by enzyme-linked immunosorbent assay （ELISA）， pyroptosis-related protein expression was detected by immunofluorescence and Western blot， and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction （Real-time PCR）. The mice were randomly divided into the blank group， model group， Qiju Dihuang Wan low-， medium-， and high-dose groups （11， 22， 44 g·kg^-1·d^-1）， and calcium dobesilate group （0.13 g·kg^-1·d^-1）. Except for the blank group， all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling， the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily， while the blank group and model group received an equal volume of normal saline， for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography， optical coherence tomography angiography， and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3， Caspase‑1， GSDMD， IL‑1β， and IL‑18 in retinal tissue， and Western blot was used to detect the protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N. ResultsCell experiments showed that compared with the blank group， the model group showed significantly decreased HRMEC viability （P<0.01）， and significantly increased levels of IL-1β， IL-18， as well as increased protein expression of NLRP3， cleaved Caspase-1， and GSDMD-N （P<0.01）. Compared with the model group， the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups （P<0.05， P<0.01）. Animal experiments showed that compared with the blank group， the model group had elevated blood glucose （P<0.01）， decreased retinal thickness and vascular density （P<0.01）， up‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β and IL‑18 in retinal tissue （P<0.01）， and up‑regulated protein expression of NLRP3， ASC， cleaved Caspase‑1 and GSDMD‑N （P<0.01）. Compared with the model group， the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose （P<0.01）， increased retinal thickness and vascular density （P<0.01）， alleviated retinal pathological damage， and down‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β， IL‑18， as well as protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N （P<0.05， P<0.01）. ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.

ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy （DR） and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D （NLRP3/Caspase-1/GSDMD） signaling pathway. MethodsHuman retinal microvascular endothelial cells （HRMEC） were divided into the blank group， model group， and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group， all groups were induced with 40 mmol·L^-1 high glucose， and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum， respectively， based on the induction. After 24 h of culture， the levels of interleukin （IL）-1β and IL-18 were measured by enzyme-linked immunosorbent assay （ELISA）， pyroptosis-related protein expression was detected by immunofluorescence and Western blot， and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction （Real-time PCR）. The mice were randomly divided into the blank group， model group， Qiju Dihuang Wan low-， medium-， and high-dose groups （11， 22， 44 g·kg^-1·d^-1）， and calcium dobesilate group （0.13 g·kg^-1·d^-1）. Except for the blank group， all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling， the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily， while the blank group and model group received an equal volume of normal saline， for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography， optical coherence tomography angiography， and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3， Caspase‑1， GSDMD， IL‑1β， and IL‑18 in retinal tissue， and Western blot was used to detect the protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N. ResultsCell experiments showed that compared with the blank group， the model group showed significantly decreased HRMEC viability （P<0.01）， and significantly increased levels of IL-1β， IL-18， as well as increased protein expression of NLRP3， cleaved Caspase-1， and GSDMD-N （P<0.01）. Compared with the model group， the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups （P<0.05， P<0.01）. Animal experiments showed that compared with the blank group， the model group had elevated blood glucose （P<0.01）， decreased retinal thickness and vascular density （P<0.01）， up‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β and IL‑18 in retinal tissue （P<0.01）， and up‑regulated protein expression of NLRP3， ASC， cleaved Caspase‑1 and GSDMD‑N （P<0.01）. Compared with the model group， the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose （P<0.01）， increased retinal thickness and vascular density （P<0.01）， alleviated retinal pathological damage， and down‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β， IL‑18， as well as protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N （P<0.05， P<0.01）. ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.

The incidence of age-related macular degeneration(AMD)is rising with the intensifying aging trend,be-coming a critical challenge that demands urgent solutions.Dry AMD(dAMD)accounts for approximately 80％of all AMD cases,and there is currently a lack of highly effective treatment options.In recent years,traditional Chinese medicine(TCM)has been proven to effectively treat dAMD through actions such as antioxidation,anti-apoptosis,anti-inflammation,and lipid-lowering.By reviewing domestic and international literature,this article discusses TCM monomers,extracts,and compound formulations for dAMD,analyzing their various mechanisms.Based on traditional TCM efficacy theories and in-tegrated with modern mechanisms of action,it targets the active components of TCM to elucidate the connection between effective medicinal targets of TCM and dAMD,thereby clarifying the efficacy and scientific basis of TCM monomers,com-pounds,and extracts in treating dAMD.The aim is to provide new perspectives for the prevention and clinical treatment of dAMD.

The incidence of age-related macular degeneration(AMD)is rising with the intensifying aging trend,be-coming a critical challenge that demands urgent solutions.Dry AMD(dAMD)accounts for approximately 80％of all AMD cases,and there is currently a lack of highly effective treatment options.In recent years,traditional Chinese medicine(TCM)has been proven to effectively treat dAMD through actions such as antioxidation,anti-apoptosis,anti-inflammation,and lipid-lowering.By reviewing domestic and international literature,this article discusses TCM monomers,extracts,and compound formulations for dAMD,analyzing their various mechanisms.Based on traditional TCM efficacy theories and in-tegrated with modern mechanisms of action,it targets the active components of TCM to elucidate the connection between effective medicinal targets of TCM and dAMD,thereby clarifying the efficacy and scientific basis of TCM monomers,com-pounds,and extracts in treating dAMD.The aim is to provide new perspectives for the prevention and clinical treatment of dAMD.

Objective To investigate the predictive value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for invasiveness of hilar cholangiocarcinoma (HC).Methods The retrospective casecontrol study was conducted.The clinicopathological data of 65 HC patients who were admitted to the Sun Yat-sen Memorial Hospital from January 2012 to November 2017 were collected.Patients received DW MRI before treatment,and 2 senior imaging doctors analyzed imaging data and measured the apparent diffusion coefficient (ADC) for the primary lesions of HC.Observation indicators:(1) MRI situations of HC;(2) relationship between ADC and clinicopathological factors;(3) receiver operator characteristic (ROC) curve analysis;(4) treatment and follow-up situations.According to patients' conditions,treatment plans were done within 2 weeks after MRI and patients underwent radical resection of HC.Follow-up using telephone interview was performed to detect tumor recurrence up to December 2017.Measurement data with normal distribution were represented as (x)±s,and comparisons between group and among group were respectively analyzed using the t test and one-way ANOVA.Spearman's rank correlation was performed to analyze the relationship between ADC and clinicopathological factors.ROC curves assessed the diagnostic efficiency of ADC.Results (1) MRI situations of HC:MRI and magnetic resonanced cholangio-pancreatography (MRCP) in 65 patients showed varying degrees of soft rattan-like dilations of intrahepatic bile ducts and truncation signs of bile tracts in hepatic port.Of 65 patients,tumors in 23,7 and 35 patients were respectively pedunculated type,polypoid type and infiltrating type.The pedunculated-type lesions of 23 patients presented as low signal on T1WI and slightly high signal on T2WI;after enhanced scans of MRI,pedunculated-type lesions of 7 patients demonstrated moderate homogenous enhancement in 3 patients,ring-like enhancement with internal liquefaction necrosis in 10 patients and moderate heterogeneous enhancement in 10 patients,respectively.The polypoid-type lesions presented as low signal on T1WI and high signal on T2WI,and moderate homogenous enhancement by enhanced scans of MRI.There were varying degrees of bile duct wall thickness and irregular nodules in the infiltrating-type lesions of 35 patients,showing moderate enhancement by enhanced scans of MRI.All the lesions of 65 patients using DW MRI demonstrated restricted diffusion,showing a clear boundary between lesions and normal surrounding bile ducts or liver tissues;heterogeneous enhancement lesions by MRI scans presented as heterogeneously high signal on DWI and heterogeneously low signal on ADC map,and necrotic area of lesions showed low signal on DWI;homogenous enhancement by MRI scans presented as homogenously high signal on DWI and homogenously low signal on ADC map.(2) Relationship between ADC and clinicopathological factors:ADC was respectively (1.382±0.165)× 10-3 mm2/s,(1.343±0.138)× 10-3 mm2/s,(1.291-±0.226)×10-3 mm2/s,(1.111±0.243)×10-3 mm2/s in stage Ⅰ,Ⅱ,Ⅲ and Ⅳ (TNM staging) and (1.441± 0.355) × 10-3 mm2/s,(1.226 ± 0.177) × 10-3 mm2/s,(1.061 ± 0.228) × 10-3 mm2/s in highdifferentiated,moderate-differentiated and low-differentiated tumors (pathological grading) and (1.403±0.176)× 10-3 mm2/s,(1.121±0.238)× 10-3 mm2/s in Ki-67 score ≤ 10％ and ＞ 10％ and (1.115±0.241)× 10-3 mm2/s,(1.347±0.174)× 10-3 mm2/s in HC patients with and without lymph node metastasis,with statistically significant differences in the above indicators (F =4.158,9.866,t =11.607,13.464,P＜0.05).Results of Spearman's rank correlation analysis showed that ADC had a negative correlation with TNM staging,pathological grading and Ki-67 score (r=-0.532,-0.522,-0.409,P＜0.05).(3) ROC curve analysis:using 1.225×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of stage Ⅰ-Ⅱ HC and stage Ⅲ-Ⅳ HC were 70.5％ and 81.0％,and area under ROC curve was 0.705 (95％CI:0.62-0.84,P＜0.05).Using 1.100×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of lowdifferentiated HC and moderate-and high-differentiated HC were 88.2％ and 64.3％,and area under ROC curve was 0.814 [95％ confidence interval (CI):0.69-0.90,P＜0.05].Using 1.243×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of Ki-67 score ≤ 10％ and ＞ 10％ were 66.7％ and 75.0％,and area under ROC curve was 0.783 (95％CI:0.62-0.90,P＜0.05).Using 1.222×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of lymph node metastasis were 91.3％ and 71.4％,and area under ROC curve was 0.873 (95％CI:0.76-0.94,P＜0.05).(4) Treatment and followup situations:65 patients underwent successful radical resection of HC.Thirty-three patients were followed up for 1-24 months.Of 33 patients,5 had tumor recurrence within 6 months postoperatively,including 4 with ADC ＜ 1.100× 10-3 mm2/s,13 had tumor recurrence after 6 months postoperatively,and 15 didn't have tumor recurrence or metastasis,including 1 with ADC ＜ 1.100× 10-3 mm2/s.Conclusions There are different ADC in differentTNM staging,pathological grading,Ki-67 score and with or without lymph node metastasis of HC.ADC of DWMRI can be used as a preoperative imaging predictor for invasiveness of HC.

BACKGROUND: Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes in BCa and establish criteria of imaging diagnosis. METHODS: We retrospectively assessed the imaging characteristics of 191 BCa patients who underwent radical cystectomy. The data regarding size, shape, density, and diffusion of the lymph nodes on CT and/or MRI were obtained and analyzed using Kruskal-Wallis test and χ test. The optimal cutoff value for the size of metastatic node was determined using the receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 184 out of 3317 resected lymph nodes were diagnosed as metastatic lymph nodes. Among 82 imaging-detectable lymph nodes, 51 were confirmed to be positive for metastasis. The detection rate of metastatic nodes increased along with more advanced tumor stage (P < 0.001). Once the ratio of short- to long-axis diameter ≤ 0.4 or fatty hilum was observed in lymph nodes on imaging, it indicated non-metastases. Besides, lymph nodes with spiculate or obscure margin or necrosis indicated metastases. Furthermore, the short diameter of 6.8 mm was the optimal threshold to diagnose metastatic lymph node, with the area under ROC curve of 0.815. CONCLUSIONS The probability of metastatic nodes significantly increased with more advanced T stages. Once lymph nodes are detected on imaging, the characteristic signs should be paid attention to. The short diameter > 6.8 mm may indicate metastatic lymph nodes in BCa.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnostic imaging ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Staging ; Pelvic Neoplasms ; diagnostic imaging ; pathology ; secondary ; surgery ; Pelvis ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed ; Urinary Bladder Neoplasms ; diagnostic imaging ; pathology ; surgery

Objective To cstimnate the diagnostic performance of computer tomography (CT) and magnetic resonance imaging (MRI) for detecting metastasis in pelvic lymph nodes with normal size in patients with bladder cancer.Methods hnaging of CT and MRI and clinical data of 118 patients who underwent radical cystectomy and pelvic lymphadenectomy were reviewed.The diagnostic efficacy of CT and MRI were analyzed when taking lymph nodes short axis diameter ≥0.3 cm and ≥ 1.0 cm respectively as diagnostic criterion of metastasis with corTelation of pathological results.Results 22.7％ (27/118) of patients were confirmed lymph nodes malignancies among 118 patients based on pathology.Totally 1 705 lymph nodes were detected in surgery and 119 of them were observed malignancy according to pathological presentation.The malignant nodes were mainly distributed in the perivesical (35.4％,41/119),internal iliac (12.6％,15/119),external iliac (30.3％,36/119),obturator region (21.0％,25/119) and presarcal region (1.7％,2/119).Imaging of CT and MRI showed that when taking nodes with ≥0.3 cm in maximum short-axis diameter (MSAD) as positive,the sensitivity (Se),specificity (Sp),and positive predictive values (PPV) were 16.0％,99.2％,54.2％ and 56.5％,99.2％,86.7％ respectively.While taking MSAD≥1.0 cm as malignant,the Se,Sp and PPV of CT and MRI were 6.2％,99.9％,83.3％ and 13％,100％,100％ respectively.When taking MSAD ≥0.3 cm as positive,the Se and PPV between CT and MR were statistically different(P ＜ 0.001 and P =0.036,respectively).When taking MSAD ≥ 1.0 cm as positive,there was no statistically difference (P =0.275 and 1.000,respectively).Conclusions The incidence of normal-sized lymph node metastasis was higher in patients with bladder cancer.At this phase the MRI evaluation was superior to that of CT.When the MSAD ≥ 1.0 cm,there was no significant difference between CT and MRI.