Chronic refractory wound （CRW） presents significant clinical treatment challenges due to pathological characteristics such as persistent inflammation， bacterial infection， oxidative stress and inadequate angiogenesis. Astragali Radix， a traditional Chinese medicinal herb， exerts multi-target pharmacological effects on CRW through its active components， including Astragalus polysaccharides， flavonoids， and astragaloside Ⅳ， etc. Fundamental studies indicate that these components promote CRW healing by modulating inflammatory responses， inhibiting pathogen growth， improving antioxidant capacity and stimulating neovascularization. Network pharmacology and bioinformatics studies have revealed that active components of Astragali Radix target and modulate key signaling nodes such as nuclear factor-κB， phosphatidylinositol 3-kinase/Akt， AMP-activated protein kinase， and vascular endothelial growth factor receptor， as well as inflammation-angiogenesis-related pathways， thereby synergistically exerting anti-inflammatory and pro-angiogenic effect. Clinical applications have demonstrated that oral formulations （e.g.， Huangqi guizhi decoction， Danggui huangqi decoction， etc.） reduce healing time of CRW and lower inflammatory marker levels， while topical preparations （e.g.， Zizhu ointment， Huangqi shengji ointment， electrostatically spun Astragalus polysaccharide composite nanofibre dressings， etc.） significantly improve healing rates of CRW and minimize complications.

Objective To study the relationship between blood microRNA-133b(miR-133b)and solu-ble fms-like tyrosine kinase 1(sFLT1)levels with the prognosis in the patients with endometrial cancer.Methods A total of 122 patients with endometrial cancer visited in the gynecology department of this hospital from January 2015 to January 2016 were prospectively selected as the study subjects,and divided into the sur-vival group(n=58)and death group(n=64)according to the 5-year prognosis of the patients with endome-trial cancer.The miR-133b and sFLT1 levels were compared between the two groups.The COX regression was used to analyze the relationship between miR-133b and sFLT1 with the prognosis of the patients with en-dometrial cancer.Results The levels of miR-133b and sFLT1 in the survival group were higher than those in the death group,and the differences were statistically significant(P＜0.05).The median survival time in the miR-133b low-level group was shorter than that in the miR-133b high level group,and the difference was sta-tistically significant(P＜0.05).The median survival time of the sFLT1 low level group was shoeter than that in the sFLT1 high level group,and the difference was statistically significant(P＜0.05).The FIGO stageⅢ-Ⅳ and lymph node metastasis were the independent risk factors for the prognosis of endometrial cancer(P＜0.05),and the pathological G1-G2,high level of miR-133b and sFLT1 were the independent protective factors for the prognosis of endometrial cancer(P＜0.05).Conclusion The miR-133b and sFLTl low levels in the patients with endometrial cancer are associated with the disease progression,and both are the independ-ent risk factors of prognosis.

ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology. MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language. ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on. ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

Objective: To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy. Methods: This is a descriptive study of case series. Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers: Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics, surgical approach, number of dissected lymph nodes, immunohistochemical staining, and pathological staging were summarized and analyzed. The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels. Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut. Results: Thirty (0.33%, 30/8972) eligible patients, 24 (80.0%) of whom were male, were identified in the two centers. The mean age was 63.9±11.0 years. Seventeen (56.7%) of these patients had papillary or tubular adenocarcinomas, including 13 (43.3%) poorly- and four (13.3%) moderately-differentiated tumors; four (13.3%) had signet-ring cell carcinomas; four (13.3%) mucinous adenocarcinomas; three (10.0%) mixed adenocarcinomas, including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma; and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma. Two patients (6.7%) had other types of cancer, namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one. The predominant tumor sites were the lesser curvature (n=26, 86.7%) and the cardia (n=24, 80.0%). The mean tumor diameter was 6.6 cm, mean distance between tumor and esophageal resection margin was 1.5 cm, and proportions of tumor invasion into the dentate line, nerves, and vessels were 80.0% (24/30), 86.7%(26/30), and 93.3% (28/30), respectively. The mean number of lymph nodes resected was 20.4±8.9. The pathological stage was mainly T4 (n=18, 60.0%) and N3 (n=21, 70.0%), the median Ki67 was 52.7%, and the rates of positivity for HER2, EGFR, VEGFR, E-cadherin and PD-L1 were 40.0% (12/30), 46.7% (14/30), 80.0% (24/30), 86.7% (26/30) and 16.7% (5/30), respectively. At the cellular level, cancer cells were mainly distributed in small focal areas, as cell masses, or as tumor thrombi; large numbers of widely distributed atypic cells were seldom observed. At the tissue level, cancer cells were located in the mucosal layer in seven patients (23.3%), in the submucosal layer in 18 (60.0%), and in the muscular layer in five (16.7%); no cancer cells were identified in the outer membrane. Five of the seven tumors were located in the lamina propria, two in the muscularis mucosae, and none in the mucosal epithelium. Conclusion: Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index, are at a late pathological stage, and the residual cancer is mostly located in the submucosa.
Humans ; Male ; Middle Aged ; Aged ; Female ; Margins of Excision ; Adenocarcinoma/pathology* ; Carcinoma, Signet Ring Cell/pathology* ; Lymph Nodes/pathology* ; Adenocarcinoma, Mucinous/pathology* ; Stomach Neoplasms/pathology* ; Gastrectomy ; Neoplasm Staging ; Retrospective Studies

Objective:To explore the effect of alternating food restriction on blood glucose, body mass index (BMI) and blood lipids in overweight or obesity patients with type 2 diabetes mellitus.Methods:A prospective cohort study was used. Three hundred overweight or obesity type 2 diabetes mellitus patients with stable blood glucose control from December 2021 to February 2022 in Nanxiang Hospital, Jiading District of Shanghai City were selected. The patients were divided into alternating food restriction group (adopting alternating food restriction therapy, giving balanced meal plates, reducing 30% of calories intake every other day), low carbohydrate high protein group (adopting low carbohydrate and high protein therapy, giving low carbohydrate and high protein reduction meal plates, reducing 15% of calories intake every day) and balanced diet group (adopting balanced diet therapy, giving balanced meal plates) by random digits table method with 100 cases each. All three groups received intervention treatment for 6 months. The height and body mass before intervention and the end of intervention and 6 months after intervention were measured, and the BMI was calculated. The levels of glycosylated hemoglobin (HbA 1c), fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), triacylglycerol (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were measured. Results:At the end, 280 cases were completed the study. There were 90 cases in the alternating food restriction group, 90 cases in the low carbohydrate high protein group, and 100 cases in the balanced diet group. There were no statistical differences in HbA 1c, FBG, 2 h PBG, BMI, TG, TC and LDL-C before intervention among the three groups ( P>0.05). At the end of the intervention, the HbA 1c and FBG in alternating food restriction group and low carbohydrate high protein group were significantly lower than those in balanced diet group: (6.50 ± 0.39)% and (6.67 ± 0.30)% vs. (6.79 ± 0.32)%, (6.47 ± 0.61) and (6.80 ± 0.30) mmol/L vs. (6.94 ± 0.37) mmol/L, the indexes in alternating food restriction group were significantly lower than those in low carbohydrate high protein group, and there were statistical difference ( P<0.05); the 2 h PBG and BMI in alternating food restriction group and the low carbohydrate high protein group were significantly lower than those in balanced diet group: (8.83 ± 0.63) and (8.81 ± 0.70) mmol/L vs. (9.45 ± 0.85) mmol/L, (25.99 ± 2.13) and (26.53 ± 2.16) kg/m 2 vs. (27.24 ± 2.24) kg/m 2, and there were statistical differences ( P<0.05), there were no statistical differences in 2 h PBG and BMI between alternating food restriction group and the low carbohydrate high protein group ( P>0.05). Six months after intervention, the HbA 1c, 2 h PBG and BMI in alternating food restriction group were significantly lower than those in low carbohydrate high protein group and balanced diet group: (6.62 ± 0.29)% vs. (6.79 ± 0.19)% and (6.84 ± 0.23)%, (9.21 ± 0.53) mmol/L vs. (9.48 ± 0.66) and (9.55 ± 0.51) mmol/L, (25.60 ± 1.67) kg/m 2 vs. (27.26 ± 2.42) and (27.79 ± 2.49) kg/m 2, and there were statistical differences ( P<0.05), there were no statistical differences in HbA 1c, 2 h PBG and BMI between low carbohydrate high protein group and balanced diet group ( P>0.05). At the end of intervention and 6 months after intervention, there were statistical differences in TG, TC and LDL-C among the three groups ( P<0.05); among them, the TG in alternating food restriction group was significantly lower than that in low carbohydrate high protein group and the balanced diet group: (1.67 ± 0.70) mmol/L vs. (1.99 ± 0.89) and (2.49 ± 0.94) mmol/L, (1.70 ± 0.71) mmol/L vs. (2.04 ± 0.96) and (2.53 ± 1.08) mmol/L, and there were statistical differences ( P<0.05), there was no statistical difference in TG between the low carbohydrate high protein group and balanced diet group ( P>0.05). Conclusions:The alternating food restriction therapy in overweight or obesity patients with type 2 diabetes mellitus can not only reduce blood glucose, improve blood lipids, but also reduce BMI, and the overall effect is better than that of low carbohydrate high protein therapy.

Objective: To investigate the clinicopathological features, immunophenotype, ultrastructure, genetic alterations and prognosis of succinate dehydrogenase-deficient renal cell carcinoma (SDH RCC). Methods: A total of 11 SDH RCCs, diagnosed from 2010 to 2019, were selected from the Department of Pathology of Nanjing Jingling Hospital, Nanjing University School of Medicine for clinicopathologic, immunohistochemical (IHC), ultrastructural investigation and follow-up. The molecular features of seven cases were analyzed by the panel-targeted DNA next generation sequencing (NGS). Results: There were seven males and four females, with ages ranging from 24 to 62 years (mean 41.4 years, median 41 years). Microscopically, SDH RCC was mainly composed of solid and tubular structures with local cystic change. Four cases showed nested or trabecular structure distributed in a loose hypocellular connective tissue or around scar, similar to oncocytoma. The neoplastic cells demonstrated flocculent eosinophilic cytoplasm with typical intracytoplasmic vacuoles. Immunohistochemically, eight cases were negative for SDHB; three cases showed focal and weak expression, whereas normal renal tubular and vascular endothelial cells demonstrated strong cytoplasmic staining. NGS of DNA targeted-panel detected pathogenic mutations of SDHB gene in seven cases (including three cases with equivocal IHC expression of SDHB), without any mutations in other SDH related genes. There were four cases of SDHB missense mutation, one case of frameshift mutation, one case of splicing mutation, and one case of acquired stop codon mutation. Conclusions: SDH RCC is a distinct variant of RCCs with genetic tendency or with hereditary cancer syndrome. NGS is recommended to detect the related gene mutations for a definitive diagnosis. The patients should be closely followed up.
Adult ; Carcinoma, Renal Cell/genetics* ; Endothelial Cells ; Female ; Humans ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Prognosis ; Succinate Dehydrogenase/genetics* ; Young Adult

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.
Biomarkers, Tumor ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Prognosis

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Methods: Two cases of ALK-translocation renal cell carcinoma diagnosed from January 2011 to December 2020 were retrospectively analyzed to characterize their morphological features, immunohistochemical expression and prognosis. Multiple molecular studies including fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing were performed to characterize the genetic alterations. Results: Two patients included one male and one female, with 59 and 57 years old, respectively. Morphologically, case 1 resembled collecting duct carcinoma or renal medullary carcinoma, which demonstrated tubular, microcapsule and reticular structures, with a remarkable myxoid background and lymphocytes infiltration; case 2 resembled Xp11.2 translocation renal cell carcinoma or type 2 papillary renal cell carcinoma, which demonstrated tubular papillary and focal solid structures, with flocculent cytoplasm and many foamy histiocytes, but without myxoid background and lymphocytes infiltration. Immunohistochemistry showed strongly positive expression of ALK. CK7, E-cadherin, vimentin, PAX8 and CD10 showed various degrees of expression, and other antibodies were nonreactive. A variety of molecular assays showed definite ALK gene translocation, with rare VCL-ALK gene fusion (VCL exon and 16-ALK exon 20) in case 1, and EML4-ALK gene fusion (EML4 exon and 2-ALK exon 20) in case 2. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma.
Anaplastic Lymphoma Kinase/genetics* ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Lung Neoplasms ; Male ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies

Humans ; Liposarcoma/genetics* ; Liposarcoma, Myxoid/genetics* ; Transcription Factor CHOP/genetics*