Applications of Data Characteristic AI-Assisted Raman Spectroscopy in Pathological Classification.

Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.

Clinical and Endoscopic Features of Pneumatosis Cystoides Intestinalis: A Retrospective Study in 192 Patients.

BACKGROUND/AIMS: Pneumatosis cystoides intestinalis is not well recognized. Clinical features vary in several case reports, and prognosis remains unclear. We aimed to summarize the clinical and endoscopic features of pneumatosis cystoides intestinalis and to explore potential factors associated with lesion size. MATERIALS AND METHODS: We retrospectively collected clinical and endoscopic features of patients diagnosed with pneumatosis cystoides intestinalis from July 2015 to October 2021. Patients were allocated to 2 groups according to lesion size with 2 cm as boundary value. Baseline characteristics were compared between the groups. RESULTS: A total of 192 patients were included in this study with a 1.3:1 male-to-female ratio. About 91 lesions (47.70%) were ≥2 cm and those patients were more likely to have a history of polypectomy or abdominal surgery compared to lesion size <2 cm (P < .05). For 50 patients who received follow-up colonoscopy, 28 cases (56.00%) disappeared spontaneously and 22 cases (44.00%) remained unchanged. No factors have been observed to be connected with prognosis. CONCLUSIONS: Colonoscopy is beneficial to the diagnosis of pneumatosis cystoides intestinalis. Patients with a history of polypectomy or abdominal surgery were more likely to develop lesions <2 cm. Most patients do not need special treatments and have favorable prognosis.

Fabrication of human serum albumin-imprinted photothermal nanoparticles for enhanced immunotherapy.

Photothermal nanoparticles have been confirmed to induce an antitumor immune response and turn "cold tumor" into "hot tumor". However, their delivery efficacy to tumors is limited by the elimination from the reticalendothel system. Herein, human serum albumin (HSA)-imprinted polymer coated Fe3O4 nanoparticles (Fe3O4@MIPs) are fabricated by oxidative polymerization of dopamine in the presence of HSA on the polydopamine pre-modified Fe3O4 nanoparticle surface, followed by the removal of HSA. The Fe3O4@MIPs exhibit rapid and specific reabsorption toward HSA. The molecularly imprinted sites on the Fe3O4@MIPs endow it with an albumin-rich protein corona in the blood and result in less elimination from the reticalendothel system than non-albumin-imprinted particles (Fe3O4@NIPs). Moreover, the molecularly imprinted polymer, which consists of polydopamine, also improves the photothermal effect of Fe3O4 nanoparticles. In vivo, the albumin camouflage in Fe3O4@MIPs produces a 2.6-fold improvement in tumor accumulation in comparison to Fe3O4@NIPs, and more heat is produced upon 808 nm laser irradiation, which further triggers an efficient immunogenic cell death (ICD) progress. Thus, the combination of Fe3O4@MIPs and PD-L1 antibody can not only inhibit the growth of primary tumors but also eliminates lung metastasis by eliciting immunological effect.

Electroacupuncture improves behavioral recovery and increases SCF/c-kit expression in a rat model of focal cerebral ischemia/reperfusion.

This study aims to investigate the mechanism of electroacupuncture (EA) in promoting behavioral recovery after focal cerebral ischemia/reperfusion. The SD rats received filament occlusion of the right middle cerebral artery for 2 h followed by reperfusion for 1, 3, 7, 14, and 21 days, respectively. Rats were randomly divided into sham group, model group and EA group. After 2 h of the reperfusion, EA was given at bilateral "Hegu" point (LI 4) in the EA group. Neurobehavioral evaluation, the expression of stem cell factor (SCF), its receptor c-kit and matrix metalloproteinase-9 (MMP-9) protein and mRNA in the cortical ischemic region were measured. EA treatment can improve behavioral recovery after ischemia/reperfusion. Compared with the sham group, the positive cells and mRNA expression of SCF, c-kit, MMP-9, the protein expression of SCF were increased significantly in the model and EA groups (P < 0.001). Compared with the model group, the positive cells, protein and mRNA expression of SCF were increased significantly in EA groups (P < 0.01). The positive cells and mRNA expression of c-kit were increased in EA groups beginning at 3 day and remained significantly high thereafter. The expression of MMP-9 positive cells and mRNA were deceased significantly in the 1 day subgroup in EA (P < 0.01), but increased significantly in the 3, 7 days subgroups (P < 0.01). We conclude that EA treatment up-regulates the positive cells and mRNA expression of SCF, c-kit and MMP-9 after cerebral ischemia/reperfusion. EA may promote neurobehavioral recovery by increasing the protein and mRNA expression of SCF, c-kit and MMP-9 after cerebral ischemia/reperfusion.

Clinical application of magnetic resonance imaging in preoperative evaluation of endometrial cancer.

OBJECTIVE: To investigate the value of magnetic resonance imaging (MRI) in the preoperative assessment of endometrial cancer. METHODS: Ninety-four patients with histopathologically confirmed endometrial carcinoma were retrospectively enrolled in this study. MRI findings were compared with the pathologic findings in all cases. The depth of myometrial invasion and lymph node metastasis were evaluated by T2 weighted imaging (T2WI) combined with contrast enhancement or diffusion weighted imaging (DWI). RESULTS: Among these 94 patients,62 had no or superficial myometrial involvement and 32 cases had deep myometrial involvement. Meanwhile, 24 groups of metastatic lymph nodes and 164 groups of non-metastatic lymph nodes were detected. The accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of T2WI combined with contrast enhancement in discriminating no/superficial myometrial involvement from deep myometrial involvement were 88.3%, 90.3%, 84.4%, 91.8%, and 81.8%, whereas those of T2WI combined with DWI were 81.9%, 87.1%, 71.9%, 85.7%, and 74.2%, respectively. The accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of T2WI combined with contrast enhancement in identifying metastatic lymph nodes were 89.4%, 96.8%, 54.5%, 90.9%, and 78.3%, whereas those of T2WI combined with DWI were 91.5%, 95.5%, 72.7%, 94.3%, and 77.4%, respectively. CONCLUSIONS: T2WI combined with contrast enhancement is superior to T2WI combined with DWI in evaluation of the depth of myometrial invasion. However, DWI is more sensitive in identifying lymph node metastasis than T2WI combined with contrast enhancement.

[Effects of electroacupuncture on endothelial progenitor cells in peripheral blood and bone marrow in local cerebral ischemia/reperfusion rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) of "Hegu" (LI 4) on blood stromal cell-derived factor 1alpha (SDF-1alpha), CXC chemokine receptor 4+ (CXCR 4+) positive cells and endothelial progenitor cells (EPCs) and bone marrow (BM) EPCs levels in local cerebral ischemia/reperfusion injury (CI/IR) rats, so as to study its mechanisms underlying improvement of cerebral ischemia. METHODS: A total of 54 SD rats were randomly divided into normal control, model, and EA groups. The latter two groups were further divided into 1 d, 2 d, 3 d and 7 d subgroups (4 time-points), respectively. CI/RI model was established by occlusion of the middle cerebral artery. EA (40 Hz/60 Hz, 1-2 mA) was applied to bilateral "Hegu" (LI 4) for 15 min, once daily, 1, 2, 3 and 7 days, respectively. Flow cytometer was used to detect the counts of EPCs and CXCR 4+ cells in the peripheral blood, and BM EPCs. Serum SDF-1alpha was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the percentages of blood EPCs and CXCR 4+ cells and BM EPCs, and serum SDF-1alpha content on the 1st day, and the percentage of blood CXCR 4+ cells on the 2nd day were increased significantly in the model group (P<0.01, P<0.05). In comparison with the model group, percentages of blood EPCs and CXCR 4+ cells on the 1st day of EA group were reduced significantly (P<0.01), but the percentage of blood EPCs on the 2nd day, those of blood CXCR 4+ cells on the 2nd day and 3rd day, serum SDF-1alpha content on the 2nd day, and the percentage of BM EPCs on the 2nd day in the EA group were all up-regulated significantly (P<0.05, P<0.01). No significant differences were found among the 3 groups in blood EPCs percentages on the 3rd day and 7th day, in blood SDF-1alpha content and BM EPCs percentage on the 7th day (P>0.05). CONCLUSION: Generally, 2 days' EA of LI 4 can up-regulate the percentages of blood and BM EPCs and blood CXCR 4+ cells as well as blood SDF-1alpha protein content in CI/RI rats, which may contribute to its effect in improving cerebral ischemia.

Anti-tumor activity and mechanisms of a novel vascular disrupting agent, (Z)-3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410).

Vascular disrupting agents (VDAs) have emerged as a new kind of anti-cancer drug in recent years. Structural modification of an active parent compound is an effective approach to developing new agents with more activity and fewer adverse reactions. In our study, six synthesized stilbene derivatives were screened for their cytotoxic activity against human tumor cells, and their mechanisms of action were investigated. The MTT assay was used to determine the anti-proliferative activity of these compounds. Polymerization of tubulin was detected by a tubulin assembly assay, and the cellular microtubule network was observed by immunocytochemical analyses. Cell-cycle distribution was detected by flow cytometry. A nude mouse model with xenografted colon cancer was used to demonstrate the in vivo anti-tumor activity, and microvessel density (MVD) was determined by immunohistochemistry. The expression levels of protein and mRNA were detected by Western blot and RT-PCR, respectively. Among the six newly synthesized compounds, (Z)-3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410) showed potent cytotoxic activity toward proliferating tumor cells and exhibited a similar cytotoxicity against multi-drug resistant (MDR) tumor cells. M410 inhibited bovine brain tubulin polymerization in a way similar to that of colchicine. In proliferating human umbilical vein endothelial cells (HUVECs), 20 nM of M410 induced cellular tubulin depolymerization within 4 h, which led to M phase arrest. Systemic administration of M410 at nontoxic doses in nude mice resulted in inhibition of tumor growth of human colon cancer LoVo xenografts. The tumor vessel density also decreased after M410 treatment, as determined by immunohistochemical staining for CD31. M410 downregulated hypoxia-inducible factor-1 alpha (HIF-1α) expression, reduced nuclear HIF-1α, and downregulated vascular endothelial cell growth factor (VEGF) mRNA. Our results indicate that M410 is a potent microtubule inhibitor that is cytotoxic, angiogenesis inhibiting and vascular targeting.

Efficient synthesis of natural polyphenolic stilbenes: resveratrol, piceatannol and oxyresveratrol.

The practical synthesis of important natural polyphenolic stilbenes, including resveratrol, piceatannol and oxyresveratrol, through Perkin methodology is described. Starting from 3,5-dihydoxyacetophenone (1), the common intermediate 3,5-dimethoxyphenylacetic acid (3) can be obtained via methylation and Willgerodt-Kindler reaction. Perkin condensations between (3) and substituted phenylaldehydes 4 furnished E-2,3-diarylacrylic acids 5, followed by decarboxylation in Cu/quinoline giving stilbene intermediates 6 which bear the Z-configuration. Finally, through a simultaneous demethylation/isomerization process in AlI3/CH3CN system, the target compounds 7a-c can be obtained respectively in good to high overall yields. The synthetic method proved to be more concise, trans-specific, mild, economical and commonly applicable.

[Effects of emodin on expression of cytokines induced by lipopolysaccharide in corneal fibroblasts].

OBJECTIVE: To investigate the effects of emodin on expression of cytokines induced by lipopolysaccharide (LPS) in cultured human corneal fibroblasts in vitro. METHODS: Primary human corneal fibroblasts of passages 4 were used in this research. Cells were treated with 10 microg/L LPS for 1, 2, 4, or 8 hours, which were pretreated with or without emodin for 30 minutes before LPS challenge. The degeneration of inhibitor of kappaB-alpha (I kappaB-alpha) and the effect of emodin on it were analyzed by Western blot analysis with a specific antibody. The cellular abundance of the mRNA of interleukin (IL)-6 and IL-8 from corneal fibroblasts under different conditions was determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Compared with cells without LPS treatment, I kappaB-alpha level significantly decreased in every time point after LPS challenge (P < 0.01). Emodin inhibited the LPS-induced degeneration of I kappaB-alpha by corneal fibroblasts in a dose-dependent manner (P < 0.05). Compared with cells without LPS treatment, the expressions of IL-6 and IL-8 mRNA significantly increased in every time point after LPS challenge (P < 0.01). At the same time, the expressions of the mRNA of IL-6 and IL-8 induced by LPS in corneal fibroblasts were also inhibited by emodin in a dose-dependent manner (P < 0.05). CONCLUSION: Emodin can inhibit the expressions of IL-6 and IL-8 mRNA induced by LPS in corneal fibroblasts, which maybe via inhibiting the degeneration of I kappaB-alpha and suppressing the activation of nuclear factor-kappaB.

Application of whole body diffusion weighted MR imaging for diagnosis and staging of malignant lymphoma.

OBJECTIVE: To evaluate the clinical impact of whole body diffusion weighted imaging (WB-DWI) on diagnosis and staging of malignant lymphoma. METHODS: Thirty-one patients with suspected lymphadenopathy were enrolled. WB-DWI was performed by using short TI inversion recovery echo-planar imaging sequence with free breathing and built-in body coil. Axial T2-weighted imaging images of the same location were used as reference. The results of WB-DWI were compared with pathological results and other imaging modalities. The mean apparent diffusion coefficient (ADC) values of different kinds of lymph nodes were compared. RESULTS: WB-DWI was positive in all 18 cases with lymphoma, 5 cases with metastatic lymph nodes and 4 of 8 cases with benign lymphadenopathy. The mean ADC value of lymphomatous, metastatic and benign lymph nodes was (0.87 +/- 0.17) x 10(-3), (0.98 +/- 0.09) x 10(-3) and (1.20 +/- 0.10) x 10(-3) mm2/s. There was significant difference in ADC value between benign lymph nodes and other two groups (P < 0.01). The sensitivity, specificity and accuracy of WB-DWI in diagnosis of lymphoma were 100% (18/18), 30.8% (4/13) and 71.0% (22/31). When an ADC value of 1.08 x 10(-3) mm2/s was used as the threshold value for differentiating malignant from benign lymph nodes, the best results were obtained with sensitivity of 87.8% and specificity of 91.3%. Sixteen of eighteen cases (88.9%) of lymphoma were accurately staged in accordance with clinical staging. CONCLUSIONS: WB-DWI is a sensitive, but less specific technique for diagnosis of lymphoma. It is difficult to differentiate lymphomatous from metastatic lymph nodes using WB-DWI. However, it is a valuable imaging modality for staging of patients with malignant lymphoma.

Clinical application of body diffusion weighted MR imaging in the diagnosis and preoperative N staging of cervical cancer.

OBJECTIVE: To evaluate the clinical impact of body diffusion weighted imaging (DWI) on the diagnosis and preoperative N staging of cervical cancer. METHODS: Twenty-four patients (mean age 37.9 years old) with proved cervical cancer by cervical biopsy and 24 female patients with other suspected pelvic abnormalities received preoperative body DWI scan. Results of body DWI were compared with pathological findings. The apparent diffusion coefficient (ADC) values of normal cervix and different pathological types of cervical cancer were compared. ADC value of normal or inflammatory lymph nodes was also compared with that of metastatic ones. Student's t test was used for statistical analysis. RESULTS: There were 5 adenocarcinomas and 19 epitheliomas showed with biopsy results, and DWI showed 21 cervical lesions out of them (87.5%). ADC values of the normal cervix (n = 24), epithelioma (n = 19), and adenocarcinoma (n = 5) were (1.73 +/- 0.31) x 10(-3), (0.88 +/- 0.22) x 10(-3), and (1.08 +/- 0.12) x 10(-3) mm2/s, respectively. Statistical analysis showed significant difference in ADC value between normal cervical tissue and either tumor tissues (both P < 0.01). In patients had lymphadenectomy (n = 24), totally 67 lymph nodes including 16 metastatic lymph nodes were pathologically analyzed, and DWI showed 66 (98.5%) out of them. ADC values of normal/inflammatory and metastatic lymph nodes were (1.07 +/- 0.16) x 10(-3) and (0.77 +/- 0.13) x 10(-3) mm2/s (P < 0.01). Receiver operating characteristic (ROC) curve of ADC value of metastatic lymph node showed that area under curve was 0.961. CONCLUSIONS: ADC value in cervical carcinoma is lower than that in normal cervix, and ADC may have predictive value in subtype discrimination. ADC value may improve the preoperative characterization of lymph node metastasis. And at least abdominal and pelvic DWI scan is suggested for N staging evaluation in such patients.

Experimental study of inflammatory and metastatic lymph nodes with diffusion weighted imaging on animal model: comparison with conventional methods.

OBJECTIVE: To investigate the feasibility of magnetic resonance (MR) diffusion weighted imaging (DWI) in discriminating inflammatory from VX2 carcinoma metastatic lymph nodes in rabbit model. METHODS: Twenty New Zealand white rabbits were randomly divided into 2 groups. Complete Freund's adjuvant was injected into the bilateral dorsal footpads to set up ipsilateral lymphadenitis model (n = 10), and the other 10 rabbits received a subcutaneous implantation of VX2 tumor cell suspension (1.5 x 10(7) cells/mL) in both thighs to set up metastatic lymph node model. MR imaging scan covering the popliteal fossa and iliac fossa including short time inversion recovery echo-planar imaging DWI (STIR-EPI-DWI), T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) was performed 2 weeks after injection. T2WI signal intensity (SI), DWI SI, long/short axial ratio (LSR) and apparent diffusion coefficient (ADC) values of the lymph nodes were evaluated in all cases. Right after MR imaging scan, popliteal and iliac fossa lymph nodes were collected for hematoxylin-eosin staining. RESULTS: Totally 33 lymph nodes larger than 5 mm, including 22 inflammatory and 11 metastatic ones, were successfully isolated and taken into pathological analysis. LSR showed no significant difference between the inflammatory and malignant lymph nodes (P > 0.05). Both benign and malignant lymph nodes appeared iso-intense on T1WI and hyperintense on both T2WI and DWI images with an even lower T1WI and higher T2WI SI core at the hilum. Both T2WI and DWI SI showed no significant difference between two pathological groups (P > 0.01) in popliteal fossa. The mean ADC value of inflammatory nodes [(1.199 +/- 0.281) x 10(-3) mm2/s] was significantly higher than that of metastatic nodes [(0.858 +/- 0.090) x 10(-3) mm2/s, P < 0.01]. On ADC map, a high ADC value central area could be seen in most of the lymph nodes no matter benign or malignant. ADC value gave out the largest area under curve (AUC(ADC) = 0.955) compared with other three indexes (AUC(LSR) = 0.488; AUC(T2WI SI)= 0.727; AUC(DWI SI) = 0.822) and gave the best sensitivity and specificity in lymph node differential diagnosis compared with the other three indexes. CONCLUSIONS: High quality DWI image can be obtained using STIR-EPI-DWI sequence in rabbit model. DWI is a new promising technique for differentiating inflammatory from metastatic lymph nodes. Compared with routine MR sequence, DWI could provide more useful physiological and functional information for diagnosis.