Objective To explore the diagnostic value of endoscopic grading of gastric intestinal metaplasia (EGGIM) score under acetic acid-enhanced narrow band imaging (AA-NBI) observation mode for gastric intestinal metaplasia (GIM). Methods A total of 120 patients who underwent gastroscopy at Jinshan Hospital of Fudan University from February 2022 to February 2023 were selected. All patients underwent both white light and AA-NBI endoscopy, with photographic records of intestinal metaplasia in five areas: greater curvature of antrum, lesser curvature of antrum, greater curvature of corpus, lesser curvature of corpus and incisura. EGGIM score was performed: 0 for no intestinal metaplasia, 1 point for focal intestinal metaplasia (GIM area ratio≤30%), 2 points for extensive intestinal metaplasia (GIM area ratio＞30%), with a total score of 10 points. Targeted biopsies were performed on suspicious GIM lesions found during endoscopy. If no suspicious GIM lesions were observed, random biopsies were performed according to the updated Sydney system. The pathological histological examination results were staged based on the operative link on gastric intestinal metaplasia assessment (OLGIM) system. The diagnostic value of EGGIM score for OLGIM stage Ⅲ-Ⅳ patients was evaluated using receiver operating characteristic (ROC) curves. Results The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of AA-NBI in detecting GIM were 96.3%, 91.6%, 94.5%, 95.0%, and 93.6%, respectively. The area under the ROC curve for EGGIM diagnosing OLGIM stage Ⅲ-Ⅳ was 0.952 (95%CI 0.914-0.990). The optimal cut-off value for EGGIM was 5 points, with a sensitivity of 96.7% (95%CI 87.6%-99.4%) and specificity of 88.1% (95%CI 76.5%-94.7%). Conclusions EGGIM score (≥5 points) under AA-NBI mode has good diagnostic capability for patients with OLGIM stage Ⅲ-Ⅳ.

Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters，such as R.E.N.A.L.，PADUA，C-Index，which are used to guide the clinical selection of surgical modalities，and predict perioperative complications and prognosis. In this paper，various scoring systems are grouped into three major categories according to their functions：prediction of surgical complexity，prediction of complications，and prediction of prognosis. The contents，characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists，enhance their surgical decision-making ability，and improve the clinical outcomes.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

The repair of the periodontal membrane is essential for the successful management of periodontal disease and dental trauma. Emdogain^® (EMD) is widely used in periodontal therapy due to its ability to promote repair. Despite substantial research, the cellular and molecular mechanisms underlying EMD's effects, particularly at the single-cell resolution, remain incompletely understood. This study established a delayed tooth replantation model in rats to investigate these aspects. Tooth loss rate and degree of loosening were evaluated at 4 and 8 weeks. Micro-CT, HE staining, TRAP staining, and immunofluorescence staining were evaluated to assess EMD's efficacy. Single-cell sequencing analyses generated single-cell maps that explored enrichment pathways, cell communication, and potential repair mechanisms. Findings indicated that EMD could reduce the rate of tooth loss, promote periodontal membrane repair, and reduce root and bone resorption. Single-cell analysis revealed that EMD promotes the importance of Vtn+ fibroblasts, enhancing matrix and tissue regeneration functions. Additionally, EMD stimulated osteogenic pathways, reduced osteoclastic activity, and promoted angiogenesis-related pathways, particularly bone-related H-type vessel expression in endothelial cells. Gene modules associated with angiogenesis, osteogenesis, and odontoblast differentiation were identified, suggesting EMD might facilitate osteogenesis and odontoblast differentiation by upregulating endothelium-related genes. Immune cell analysis indicated that EMD did not elicit a significant immune response. Cell communication analysis suggested that EMD fostered pro-regenerative networks driven by interactions between mesenchymal stem cells, fibroblasts, and endothelial cells. In conclusion, EMD proves to be an effective root surface therapy agent that supports the restoration of delayed replantation teeth.
Animals ; Tooth Replantation/methods* ; Rats ; Dental Enamel Proteins/pharmacology* ; Single-Cell Analysis ; Rats, Sprague-Dawley ; X-Ray Microtomography ; Osteogenesis/drug effects* ; Male ; Periodontal Ligament/drug effects*

Objective To evaluate the efficacy and safety of modified pelvic floor reconstruction in non-nerve-sparing robot-assisted radical prostatectomy (NNS RARP) for improving postoperative urinary control. Methods A retrospective analysis was conducted on the clinical data of 79 prostate cancer patients who underwent NNS RARP at Tangdu Hospital during Jan.2020 and Dec.2023, including 29 in the reconstruction group, and 50 in the non-reconstruction group. The baseline characteristics including age, body mass index, prostate-specific antigen (PSA) level, clinical stage, prostate volume, and biopsy Gleason score, and perioperative indexes including operation time, intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins were compared between the two groups. Additionally, urinary continence function was assessed before operation and 1,3,6, and 12 months after operation using the international consultation on incontinence questionnaire-short form (ICIQ-SF) and the incontinence quality of life questionnaire score (I-QoL). Results No statistically significant differences were observed in the baseline characteristics between the two groups (P>0.05). The operation time was significantly longer in the reconstruction group than in the non-reconstruction group [ (110.24±15.08) min vs. (101.80±9.89) min, P=0.010]. There were no significant differences in intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins between the two groups (P>0.05). The reconstruction group demonstrated significantly lower ICIQ-SF scores at 1 month [ (10.17±2.16) vs. (11.56±1.66), P=0.002],3 months [ (7.62±1.29) vs. (9.52±1.80), P<0.001], and 6 months postoperatively [ (4.93±1.22) vs. (6.18± 1.67), P=0.001]compared to the non-reconstruction group (adjusted P<0.0125). Conversely, the I-QoL scores were significantly higher in the reconstruction group at 1 month [ (73.32±10.30) vs. (63.88±9.55), P<0.001]and 3 months postoperatively [ (78.91±4.82) vs. (75.66±5.17), P=0.007] (adjusted P<0.0125). However, no significant differences were found in ICIQ-SF or I-QoL scores between the two groups preoperatively and 12 months postoperatively (adjusted P>0.0125). Conclusion The application of modified pelvic floor reconstruction technique in NNS RARP is safe and feasible. Although it slightly prolongs the operation time, it does not increase surgical risks; instead, it effectively promotes early recovery of postoperative urinary continence, thereby significantly enhancing patients'quality of life.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Objective To discuss the clinical features,differential diagnosis and complication treatment of a patient with genetic visceral myopathy.Methods Medical history,physical examination and laboratory results of the patient were collected in detail.The pathology of previous surgery was reviewed.The patient's peripheral blood DNA was extracted and submitted for whole-exome sequencing.Subsequent Sanger sequencing was used to complete the pedigree verification of the mutation site.Results The patient was a young female presented with repeated in-complete intestinal obstruction since early childhood.She used to be misdiagnosed as Hirschsprung's disease for a long period and underwent multiple gastrointestinal segment resections.Her intestinal obstruction symptoms were temporarily relieved by surgeries,but severe diarrhea,mucus and bloody stools and malnutrition gradually occurred after the last operation.The patient had bacterial overgrowth in small intestinal tract and followed by intestinal op-portunistic infections secondary to chronic intestinal pseudo-obstruction.The symptoms improved after anti-infection and enteral element diet treatment.Further pathological consultation and whole-exome gene sequencing confirmed the diagnosis of visceral myopathy related to ATCG2 R148L mutation.Conclusions Patients with early onset of chronic intestinal pseudo-obstruction and have poor response to conventional treatment are recommended to perform genetic test.The patients with hereditary visceral myopathy are susceptible to opportunistic intestinal infection.At-tentions should also be paid to the prevention and treatment of complications to avoid unnecessary surgery.

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg^-1）， medium- （5.85 g·kg^-1）， and low-dose （2.93 g·kg^-1） Youguiwan， and aminophylline （0.054 g·kg^-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

BACKGROUND:Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE:To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroid-induced osteonecrosis of the femoral head. METHODS:General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head.In addition,six femoral head specimens were collected from these patients.According to the Association Research Circulation Osseous(ARCO)staging system,serum specimens were grouped into ARCO Ⅱ,Ⅲ,and IV,while femoral head specimens were classified into ARCO Ⅲ and IV.Serum levels of malondialdehyde and superoxide dismutase 1 were measured.The protein expression of superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 in the femoral head was detected and verified by Data independent acquisition(DIA)for quantitative sequencing,western blot and alkaline phosphate detection. RESULTS AND CONCLUSION:The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age,sex and necrotic side.The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage Ⅲ compared with those with ARCO stage Ⅱ and IV.The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox.The levels of superoxide dismutase 1,glutathione peroxidase 4,and Bcl-2 in the necrotic region were lower than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.Western blot verified the results of DIA protein quantification.The alkaline phosphatase activity was lower in the necrotic region than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.In the necrotic and sclerotic regions,the function of differential proteins was also related to redox,and superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.To conclude,glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels,inducing osteoblast ferroptosis,and inhibiting osteogenic function.