ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β₁ （TGF-β₁）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β₁ was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β₁-induced NSCLC cell metastasis， EMT， and the TGF-β₁/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β₁/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β₁-induced EMT model， compared to the TGF-β₁ group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β₁/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β₁/Smad signaling pathway.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

ObjectiveThis study aims to explore risk factors for the development of major adverse cardiovascular and cerebrovascular events （MACCEs） in middle-aged and elderly patients with type 2 diabetes mellitus complicated with stable angina pectoris （T2DM-SAP） based on real-world clinical data in traditional Chinese medicine （TCM）， so as to develop a COX proportional risk prediction model and visualize the predicted results using a nomogram. MethodBased on the clinical scientific research information sharing system， the medical records of 586 T2DM-SAP patients （45-94 years old） were collected from January 2012 to December 2019， including age， gender， course of disease， major medical history， laboratory examination， tongue image， pulse image， TCM syndrome， and major treatment drugs. MACCE outcome indicators of patients were obtained by telephone follow-up and re-hospitalization records. The data was divided into a training set and a validation set according to 7∶3. In the training set， COX univariate analysis was used to determine the risk factors for MACCE in T2DM-SAP patients， and then variables were screened by forward-backward stepwise regression method， so as to establish a MACCE risk prediction model and construct a nomogram. The predictive efficacy of the model was reflected by the C-index， receiver operating characteristic （ROC） curve， calibration map， and clinical decision curve. ResultThe history of cerebrovascular disease ［Hazard ratio （HR）=1.983， 95% confidence interval （CI，1.314-2.993）］， low-density lipoprotein （LDL-C/mmol·L^-1）≥4.1［HR=2.683， 95%CI（1.461-4.925）］， dull red tongue ［HR=1.955， 95%CI（1.273-3.002）］， dull purple tongue ［HR=4.214， 95%CI（2.017-8.803）］， white thick coating ［HR=3.030， 95%CI（1.634-9.293）］， thin and weak pulse ［HR=2.233， 95%CI（1.283-3.888）］， and syndrome of wind-phlegm blocking collaterals ［HR=2.007， 95%CI（1.179-3.418）］ were found to be risk factors in middle-aged and elderly T2DM-SAP patients. Insulin ［HR=0.604， 95%CI（0.399-0.914）］， glycosidase inhibitor ［HR=0.627， 95%CI（0.409-0.962）］， and TCM treatment ［HR=0.328， 95%CI（0.214-0.503）］ were protective factors in middle-aged and elderly T2DM-SAP patients. The prediction model was constructed based on the above risk factors. The C-index of the model was 0.818 （95% CI 0.777 -0.859） in the training set and 0.814 （95% CI 0.773-0.855） in the validation set， and the change of C-index over time was plotted. The AUC of patients for 5， 10， 15 years in the training set was 0.71， 0.67， and 0.61. The AUC of patients for 5， 10， and 15 years in the validation set was 0.60， 0.68， and 0.63， respectively. The calibration map and clinical decision curves of 5， 10， 15 years were drawn in the training set and the validation set， respectively. The model was well calibrated and clinically effective. ConclusionThe history of cerebrovascular disease， LDL， dull red tongue， dull purple tongue， white thick coating， thin and weak pulse， and syndrome of wind-phlegm blocking collaterals are risk factors for MACCE in middle-aged and elderly T2DM-SAP patients， and insulin， glycosidase inhibitors， TCM treatment are protective factors for MACCE in middle-aged and elderly T2DM-SAP patients. A clinical prediction model is established accordingly. This model has good discrimination， calibration degree， and clinical effectiveness and provides a scientific basis for the prevention and treatment of MACCE in middle-aged and elderly T2DM-SAP patients.

Objective:To investigate the value of net water uptake (NWU) in predicting malignant edema (ME) in large hemispheric infarction (LHI).Methods:Fifty-six patients suffering from LHI in the General Hospital of Northern Theater Command from September 2017 to July 2018 were retrospectively analyzed, and their NWU was calculated separately. Patients were divided into two groups according to the occurrence of ME, which was defined as space-occupying infarct requiring decompressive craniectomy or death resulting from cerebral hernia in seven days from onset. The clinical characteristics were analyzed, and receiver operating characteristic (ROC) curve and respective area under curve (AUC) were used to assess the value of NWU and other factors.Results:After adjusting for atrial fibrillation, National Institutes of Health Stroke Scale scores at admission, and time from onset to imaging, multivariable analysis showed that NWU was an independent predictor of ME ( OR=1.226，95% CI 1.040-1.446, P=0.015). According to the ROC curve, NWU≥13.08% identified ME with great predictive power (AUC=0.813;sensitivity 0.64, specificity 0.94). Conclusions:NWU is an important predictor of ME in patients with LHI. It can help identify patients at risk of ME.

Objective To observe the clinical efficacy of radiofrequency ablation for treatment of discogenic lumbar spinal nerve posterior branch neuralgia after vertebral column endoscope operation. Methods Thirty-six patients with discogenic lumbar spinal nerve posterior branch neuralgia after vertebral column endoscope surgery admitted to the Affiliated Hospital of Logistics University of People's Armed Police from December 2011 to December 2017 were enrolled. According to difference in therapeutic methods, they were randomly divided into two groups, 18 cases in each group. The radiofrequency ablation group was treated with X-ray imaging guided lumbar spinal nerve posterior branch radiofrequency thermo-coagulation; the drug group received oral diclofenac sodium conservative treatment, 75 mg twice daily for 3 weeks. Both groups were followed up for 6 months, visual analogue scores (VAS) were used to evaluate the pain before and after treatment, the Oswestry dysfunction index was used to assess the degree of lumbar function recovery, and the surgical complications and adverse drug reactions were observed. Results The VAS scores in the two groups were similar before treatment; after treatment for 1 month, the VAS scores in both groups were significantly lower than those before treatment (radiofrequency ablation group: 1.83±0.71 vs. 5.67±0.77; drug group: 2.22±0.43 vs. 5.28±0.67, both P < 0.05); after treatment for 3 months and 6 months, the VAS scores were increased gradually, however, the scores of radiofrequency ablation group were significantly lower than those in the drug group (3 months was 2.00±0.59 vs. 3.39±0.70, 6 months was 2.17±0.51 vs. 3.61±0.50, both P < 0.05), moreover, the excellent and good rates of postoperative pain efficacy and of Oswestry dysfunction index improvement in the radiofrequency ablation group were significantly higher than those in the drug group [excellent and good rates of postoperative pain efficacy: 94.44% (17/18) vs. 22.22% (4/18), excellent and good rates of Oswestry dysfunction index improvement: 77.78% (14/18) vs. 44.44% (8/18), both P < 0.05]. There were no complications of infection and spinal nerve anterior branch injury in the radiofrequency ablation group, and 6 patients in the drug group presented mild gastric discomfort, which was relieved after symptomatic treatment. Conclusion The radiofrequency ablation is an effective method for treatment of discogenic lumbar neuralgia after vertebral column operation, compared with the conservative therapy, the ablation is more effective to relieve pain for a long time, promote the recovery of neural function, and the operation is safe with very few adverse reactions.

A technique of diffusive gradients in thin films (DGT) was developed for the in situ measurement of reactive phosphorus species in natural waters, sediments and potentially soils. Polyacrylamide / basic magnesium carbonate was used as the novel binding phase of DGT. Various factors, such as initial concentration, deployment time, pH and ionic strength, which may affect the adsorption of phosphate to the DGT were investigated. H2 SO4(0. 25 mol/ L, 10 mL) was used for elution of phosphate from the binding gel, and an elution efficiency of 85±5% was obtained. The DGT measurement was independent of ionic strength (0. 001-0. 05 mol/ L) and pH (4. 10-9. 15). The results indicated that the maximum adsorption capacities of DGT were limited to 20. 4 μg per disc ( T = 25℃, pH = 7. 00, [ P] = 2 mg / L). Good agreement was obtained between the measurement results of DGT method and molybdenum blue method in the P concentration from 0. 001 to 20 mg / L. The method detection limit (MDL) was 102. 4 ng / L. Field performances of DGT in synthetic seawater, the coastal seawater of Xiamen, Lake Yihai, Lake Chaohu and Nanfei River indicated that the basic magnesium carbonate-DGT method was more reliable than the commonly used ferrihydrite-DGT method.

Objective To investigate the effect of gastrointestinal Roux-en-Y gastric bypass surgery on blood sugar and insulin function of patients with type-2 diabetes mellitus.Methods Twenty-seven cases of gastric cancer patients with type-2 diabetes and undergone Roux-en-Y bypass the gastrointestinal treatment in the centre hospital of Cangzhou were selected as our subject.Body mass index (BMI),Glycosylated hemoglobin (HBA1c),Fasting and glucose (FPG),fasting insulin (FINS),Fasting C-peptide (FCP) levels were measured.Glucose (2 hPG),insulin (2 hINS) and C-peptide (2 hCP) levels were detected after 2 h for oral use 75 g glucose.Homeostasis model was applied to assess insulin resistance index (HOMA-IR).Results No significant change was seen in terms of BMI between before and after surgery.Compared to before surgery,the levels of FPG((7.58 ±0.84) mmol/L),2 hPG((10.43 ± 1.88) mmol/L),HbA1c((7.56 ± 1.15)％) and HOMA-IR(4.55 ±0.76) were lower in patients at 3 months after surgery ((9.93 ± 1.57) mtmol/L,(13.89± 2.13) mtmol/L,(9.88 ± 1.66) ％,(4.55 ± 0.76),respectively,P ＜ 0.05 or P ＜ 0.01).FPG ((6.56± 0.80) mmol/L),2 hPG ((8.57 ± 1.32) mmol/L),HbA1 c ((6.37 ± 1.24) ％),HOMA-IR (4.03 ± 0.45)of patients after 6 months were lower than that of before surgery and 3 months after surgery (P ＜ 0.05 or P＜0.01).However,the levels of FINS ((13.67 ± 1.96) mU/L),FCP((2.62 ±0.87) μg/L),2 hINS((49.91± 5.14) mU/L) and 2 hCP ((6.28 ± 1.65) μg/L) were higher in patients with 3 months after surgery compared to that of before surgery ((11.08 ± 1.69) mU/L,(1.78 ± 0.61) μg/L,(36.05 ± 4.03) mU/L,(4.28 ± 1.48) μg/L,P ＜ 0.01).Meanwhile those indices after 6 months (FINS:(15.88 ± 2.05) mU/L,FCP:(3.30 ±0.68) μg/L,2 hINS:(67.40 ±5.68) mU/L,2 hCP:(9.39 ± 1.52) μg/L) were higher than that of before surgery and 3 months after surgery(P ＜ 0.01).Conclusion Roux-en-Y gastrointestinal bypass can effectively reduce blood sugar level and improve the situation of Pancreatic Beta-cell function of gastric cancer patients with type-2 diabetes.

This article was aimed to observe the preventive effect of diabetes with atherosclerosis (AS) treated with Bie-Jia-Jian Pill (BJJP) on level of blood lipids, endothelin (ET), nitric oxide (NO), and matrix metalloproteinase-9 (MMP-9). Male SD rats were randomly divided into 5 groups, which were the blank group, model group, low-dose BJJP group, high-dose BJJP group and Xue-zhi-kang (XZK) group, to observe changes on the level of blood lipids, ET-1, NO and MMP-9 within 5 groups after 8-week administration. The results showed that compared with the blank group, the level of the content of NO in the model group was significantly decreased (P< 0.05), the level of ET-1 was significantly increased (P < 0.05). Compared with the model group, the high-dose and low-dose BJJP group as well as XZK group can significantly decrease the level of ET-1 (P< 0.05, or P< 0.01), increase content of NO (P< 0.05, or P< 0.01), and decrease the expression of MMP-9 (P< 0.05). It was concluded that the BJJP can regulate blood lipids, protect endothelial cell of blood vessels, stabilize plaques for the anti-AS effect.