Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

Neurodegenerative diseases encompass a diverse array of disorders that have a profoundly detrimental impact on human health, characterized by their intricate and multifaceted pathogenesis. In the recent past, a growing body of scientific research has begun to shed light on the critical involvement of the neuro-immune axis in the onset and advancement of these debilitating conditions. This comprehensive review article delves into the intricate composition of the neuro-immune axis, elucidating the complex mechanisms through which it exerts its influence in the context of neurodegenerative diseases. Furthermore, it explores the potential therapeutic applications of targeting the neuro-immune axis for the management and treatment of these diseases. This extensive examination aims to offer new perspectives and innovative strategies that could pave the way for more effective treatments for neurodegenerative diseases, thereby providing hope for those afflicted by these challenging conditions.
Humans ; Neurodegenerative Diseases/metabolism* ; Animals ; Neuroimmunomodulation/physiology*

ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.