Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective To compare the efficacy of stenting in the treatment of idiopathic intracranial hypertension(IIH)complicated by different types of venous sinus stenosis(VSS).Methods The clinical data of 48 patients with IIH complicated by VSS,who received stenting therapy at the First Affiliated Hospital of Zhengzhou University of China from January 2019 to September 2023,were retrospectively analyzed.According to the type of VSS,the patients were divided into intrinsic stenosis group(n=20)and the extrinsic stenosis group(n=28).The improvement of symptoms,Frisén grade of papilledema,lumbar puncture opening pressure(LPOP),trans-stenosis pressure gradient(△P)of VSS,and surgery-related complications were compared between the two groups.Results The mean age of the patients in the intrinsic stenosis group was greater than that of the patients in the extrinsic stenosis group(41.60 years vs.35.25 years,P=0.049).The length of the narrowed segment in the extrinsic stenosis group was 22.5 mm,which was significantly longer than 19.0 mm in the intrinsic stenosis group(P=0.007).The postoperative Frisén grade of papilledema in the extrinsic stenosis group was obviously lower than that in the intrinsic stenosis group(P=0.037).No statistically significant differences in the other clinical data existed between the two groups(all P＞0.05).After stenting,all of the median △P,mean LPOP,and median Frisén grade of papilledema were decreased significantly when compared with their preoperative values(all P＜0.001),and the postoperative 3-day median Frisén grade of papilledema in the extrinsic stenosis group was much lower(P=0.037).The patients were followed up for one year,the clinical symptoms of the patients in both groups were improved to varying degrees.At the time of discharge,the proportion of patients having no symptoms of papilledema in the extrinsic stenosis group was 57.1％,which was higher than 22.2％in the intrinsic stenosis group(P=0.049),and no statistically significant differences in the improvements of other symptoms existed between the two groups(all P＞0.05).There was no significant difference in the incidence of complications between the two groups(P=0.563).Conclusion Venous sinus stenting can effectively treat patients with IIH complicated by different types of VSS.

Objective To compare the clinical efficacy of medication and stenting in treating patients with idiopathic intracranial hypertension complicated by venous sinus stenosis.Methods The clinical data of 74 patients with idiopathic intracranial hypertension complicated by venous sinus stenosis,who were admitted to the First Affiliated Hospital of Zhengzhou University of China from January 2020 to June 2023,were retrospectively analyzed.The patients were divided into medication group(n=35,receiving drug therapy)and stenting group(n=39,receiving stent implantation therapy).Before and after treatment,lumbar puncture and fundus examinations were performed,and the postoperative improvements in intracranial pressure and papillary oedema were evaluated.The changes in the median papillary oedema Frisén grade and the average opening pressure of lumbar puncture were compared between the two groups during hospitalization period.The improvement degrees of the clinical symptoms determined at discharge,as well as at the 6 months and 12 months after discharge were compared between the two groups.The incidence of complications during the follow-up period in the two groups was recorded.Results The time interval from onset to treatment in the stenting group was longer than that in the medication group(2 months vs.one month,P=0.021),and the differences in the other baseline data between the two groups were not statistically significant(all P＞0.05).After treatment,different degrees of improvement were obtained in both groups(all P＞0.05).At the time of discharge,the degree of median papillary oedema in the stenting group was Frisén grade I,which was lower than Frisén grade Ⅱ in the medication group(P=0.011);the average opening pressure of lumbar puncture in the stenting group was 205.26 mm H2O,which was lower than 248.14 mm H2O in the medication group(P=0.002).The proportions of patients having no symptom or showing symptom improvement in the stenting group and in the medication group at the time of discharge were 74.4％and 45.7％respectively(P=0.017),which at the time of 6 months after discharge were 84.6％and 48.6％respectively(P=0.001)and at the time of 12 months after discharge were 87.2％and 57.1％respectively(P=0.004).No statistically significant difference in the incidence of complications existed between the two groups(10.3％and 8.6％respectively,P=1.000).Conclusion For the treatment of patients with idiopathic intracranial hypertension complicated by venous sinus stenosis,stent implantation therapy is superior to medication therapy in quickly and effectively relieving papillary oedema,decreasing lumbar puncture opening pressure,and improving their corresponding symptoms and signs,with satisfactory patient's prognosis and clinical safety.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

OBJECTIVE To establish a rapid analytical method to identify the chemical components in Xitong preparations for the treatment of rheumatoid arthritis by ultra-high performance liquid chromatography coupled triple time-of-flight mass spectrometry(UPLC-Triple-TOF-MS/MS). METHODS The analysis was performed on an ACQUITY UPLC HSS T3 (2.1 mm×150 mm, 1.8 μm) column with the mobile phase consisting of water containing 0.1% formic acid(A) and acetonitrile containing 0.1% formic acid(B) in gradient mode at a flow rate of 0.3 mL·min−1. Data acquisition was carried out under positive and negative ion modes. The processed data was analyzed by Peakview software and compound database. The chemical components were determined by comparison with standard products, combining with the characteristic fragments in secondary MS, and those in the related literatures. RESULTS Seventy-eight compounds were identified including 20 phenylpropanoids, 33 terpenes, 19 flavonoids, 6 oxylipins, two of which might be new compounds. CONCLUSION The method can be used for rapid identification of chemical compositions in Xitong preparations, which provides basis for quality control and elucidation of phamarcodynamic material basis of Xitong pills and capsules .

This work aims to evaluate a rapid detection method of carbapenem resistance genes in blood cultures based on Xpert Carba-R and preliminarily evaluate its clinical application.Methods:Sixteen strains of Enterobacterales carrying different carbapenem resistance genes were selected to prepare simulated positive blood culture samples and Xpert Carba-R was used to directly detect carbapenem resistance genes in the simulated positive blood culture. From January 2022 to June, a prospective study was conducted on a total of 117 Enterobacteriaceae-positive blood culture samples in the First Affiliated Hospital of Nanjing Medical University. Xpert Carba-R, detecting five kinds of carbapenem resistance genes in these samples, was evaluated in sensitivity and specificity compared to polymerase chain reaction sequencing. Meanwhile clinical data of positive patients was collected for prognostic analysis. Results:Of the 16 simulated specimens, 14 strains had carbapenem resistance genes detected by Xpert Carba-R, including 8 bla KPC, 5 bla NDM and 1 bla IMP, showing 100% agreement with the known results. As of the 117 clinical specimens, 28 cases were determined to be Enterobacterales harboring carbapenem resistance genes, including 24 bla KPC, 2 bla NDM and 2 bla KPC+ bla NDM. In comparison to the PCR sequencing, the sensitivity and specificity of Xpert Carba-R were both 100% for blood culture samples, and furthermore, the detection time was significantly reduced. Of the 25 positive patients, 9 cases were treated with monotherapy and 5 cases were effective, other 16 cases received combined treatment and 12 cases were effective. A total of 17 cases were effective, 8 cases were ineffective and 3 of them died, the mortality rate was 12% (3/25). Conclusion:Xpert Carba-R can rapidly and accurately detect carbapenem resistance genes in blood culture, which can provide evidence for rational drug therapy in early clinical stage.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Objective To observe the value of stent implantation for treating idiopathic intracranial hypertension(IIH)complicated with venous sinus stenosis(VSS).Methods Data of 54 patients with IIH complicated with VSS who underwent stent implantation were retrospectively analyzed.The papillary edema grade,lumbar puncture-opening pressure(LP-OP)and trans-stenotic pressure gradient of venous sinus(ΔP)before and after stent implantation were compared,and the symptom improvement and treatment-related complications during the follow-up period were recorded.Results Totally 60 stents were successfully implanted in 54 patients.Before stent implantation,the papillary edema grade was 3(3,3),LP-OP was(391.39±92.62)mmH2O and the ΔP was 18.50(15.00,25.00)mmHg,which decreased to 1(0,1),(208.80±62.31)mmH2O and 1.25(0.88,2.55)mmHg after stent implantation,respectively,all with significant differences(all P＜0.001).Clinical symptoms improved after stent implantation in all 54 patients.At the end of follow-up,disappearance of headache,papillary edema,visual disorder,abducent nerve paralysis and tinnitus were noticed in 30(30/37,81.08%),38(38/45,84.44%),41(41/45,91.11%),8(8/10,80.00%)and 9 cases(9/10,90.00%),respectively.Treatment-related complications occurred in 4 cases(4/54,7.41%),all improved after intervention.Conclusion Stent implantation was effective and safe for treating IIH complicated with VSS.