ObjectiveTo investigate the synergistic inhibitory effect of chidamide （CHI） combined with compound Kushen injection （CKI） on breast cancer MCF-7 cells and to elucidate the potential molecular mechanisms based on transcriptomics analysis. MethodsCell proliferation was detected by the methyl thiazolyl tetrazolium （MTT） assay， and the "one belt and one line" method was adopted to screen the optimal mass concentration for synergistic effect. According to the combination index （CI） values， cells were allocated into the blank， CHI （1.6 mg·L^-1）， CKI （0.4 g·L^-1）， and CHI+CKI （1.6 mg·L^-1+0.4 g·L^-1） groups. Transwell assay was employed to examine cell migration， and flow cytometry to measure cell cycle distribution and apoptosis rate. Transcriptome sequencing （RNA-seq） and weighted gene co-expression network analysis （WGCNA） were performed to screen the key modules highly correlated with the cell inhibition rate. Candidate genes were identified by intersecting module genes with differentially expressed genes （DEGs）， followed by functional enrichment analysis. Western blot was employed to quantify the protein levels of histone deacetylase 1 （HDAC1）， protein kinase A （PKA）， cyclin-dependent kinase inhibitor 1 （p21）， cAMP response element-binding protein （CREB） and its phosphorylated form （p-CREB）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in cells of each group. ResultsCompared with the blank group， both CHI and CKI monotherapies inhibited the proliferation of MCF-7 cells in a mass concentration-dependent manner. Compared with the blank and monotherapy groups， CHI+CKI inhibited cell migration， increased the proportion of cells arrested in the G₀/G₁ phase， and elevated the apoptosis rate （P<0.01）. WGCNA identified the MEred module strongly correlated with the inhibition rate （r=0.90， P<0.01）， yielding 97 candidate genes upon intersection with DEGs. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis indicated significant enrichment of the cAMP signaling pathway. Western blot results showed that compared with the blank group， all treatment groups down-regulated the expression of HDAC1， up-regulated the expression of PKA and p21， and increased the p-CREB/CREB and Bax/Bcl-2 ratios （P<0.01）. Compared with the monotherapy groups， CHI+CKI further up-regulated the PKA and p21 expression and increased the p-CREB/CREB and Bax/Bcl-2 ratios （P<0.01）. ConclusionThe combination of CHI and CKI exerts a significant synergistic anti-tumor effect. CHI exerts epigenetic regulation by inhibiting HDAC1， which， in combination with CKI， may further contribute to the activation of the cAMP/PKA/CREB signaling pathway， leading to up-regulation of p21 expression and the Bax/Bcl-2 ratio， thereby promoting cell cycle arrest and apoptosis.

Natural product-based drug combinations (NPDCs) present distinctive advantages in treating complex diseases. While high-throughput screening (HTS) and conventional computational methods have partially accelerated synergistic drug combination discovery, their applications remain constrained by experimental data fragmentation, high costs, and extensive combinatorial space. Recent developments in artificial intelligence (AI), encompassing traditional machine learning and deep learning algorithms, have been extensively applied in NPDC identification. Through the integration of multi-source heterogeneous data and autonomous feature extraction, prediction accuracy has markedly improved, offering a robust technical approach for novel NPDC discovery. This review comprehensively examines recent advances in AI-driven NPDC prediction, presents relevant data resources and algorithmic frameworks, and evaluates current limitations and future prospects. AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
Artificial Intelligence ; Biological Products/chemistry* ; Humans ; Drug Combinations ; Drug Discovery/methods* ; Machine Learning ; Algorithms

Objective To establish the reference interval of serum non-high-density lipoprotein cholesterol(n-HDL-C)in adults in Yan'an city of Shaanxi Province and analyze the influencing factors.Methods A total of 16 921 adults from 10 towns in Yan'an City of Shaanxi Province from January to September 2023 were selected by random sampling.Age,sex,smoking,drinking,exercise,hypertension,diabetes,dyslipidemia,chronic disease,residence,eating habits,marital status,education and monthly income were investigated.Height,weight,waist circumference and blood pressure were measured.Serum triglyceride(TG),total cholesterol(TCHO),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),Apolipoprotein A1(ApoA1),Apolipoprotein B(ApoB)and lipoprotein a[Lp(a)]levels were detected,and n-HDL-C levels were calculated:n-HDL-C(mmol/L)=TCHO(mmol/L)-HDL-C(mmol/L).The 95％reference interval(P25～P97 5)was calculated according to the percentile method recommended in WS/T402-2012 Health Industry Standard of the People's Republic of China.Multivariate logistic regression was used to analyze the influencing factors of serum n-HDL-C level.Results The serum n-HDL-C levels in both males and females were not normally distributed(S=2.119,2.091,all P＜0.001).There were significant differences in serum levels of n-HDL-C among males aged＞60 years old[2.98(2.50,3.37)mmol/L],18～30 years old[2.84(2.49,3.26)mmol/L],31～40 years old[2.98(2.62,3.42)mmol/L],41～50 years old[3.10(2.62,3.47)mmol/L]and 51～60 years old[3.05(2.64,3.46)mmol/L]contrast,and the differences were significant(H=3.618～5.680,all P＜0.05).There were significant differences in serum levels of n-HDL-C among women aged 51～60 years[3.08(2.71,3.44)mmol/L],18～30 years[2.64(2.29,3.07)mmol/L],31～40 years[2.67(2.31,3.08)mmol/L]and 41～50 years old[2.94(2.58,3.29)mmol/L]contrast(H=8.161～13.445,all P＜0.001).There were significant differences in serum n-HDL-C levels among patients aged＞60 years old[2.98(2.57,3.34)mmol/L],18～30 years old,31～40 years old and 41～50 years old contrast,and the differences were significant(H=7.985～14.018,all P＜0.001).The reference interval of serum n-HDL-C level in adult population was obtained by combining the age groups with no statistical significance:males aged 18～60 years old(1.97～3.97mmol/L),＞60 years old(1.86～3.91mmol/L);females aged 18～50 years(1.82～3.74 mmol/L),＞50 years old(1.94～3.88 mmol/L).A total of 16 921 adults were divided into normal n-HDL-C group and abnormal group,and the differences of serum TG(1.02±0.31 mmol/L vs 1.24±0.37mmol/L),TCHO(3.97±1.02 mmol/L vs 4.66±1.25 mmol/L),LDL-C(2.37±0.58mmol/L vs 2.59±0.67 mmol/L)levels and age(43.55±11.52 years vs 46.27±8.13 years)between the two groups were significant(t=2.041～3.151,all P＜0.05),in which the abnormal rate of serum n-HDL-C level was 42.50％.Multivariate Logistic regression analysis showed that males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors for serum n-HDL-C levels in adults in this region(all P＜0.05).Conclusion The reference interval of serum n-HDL-C level in adults in this area was preliminarily established.Males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors of abnormal serum n-HDL-C levels in adults in this area.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Objective To observe the value of 5.0T MRI for quantifying proton density fat fraction(PDFF)of liver.Methods Liver chemical shift encoded(CSE)MR scanning were prospectively performed using 5.0T,3.0T and 1.5T scanner in 30 volunteers,respectively,and CSE-PDFF were measured.Then MR spectroscopy(MRS)were performed using 5.0T and 1.5T scanner,respectively,and MRS-PDFF were also measured.The consistency of liver PDFF measured on different images was observed,and the value of 5.0T MRI for liver PDFF was analyzed.Results The overall consistencies of liver CSE-PDFF measured with 5.0T,3.0T and 1.5T MR scanner were all good(all ICC＞0.75,all P＜0.001).The consistency of liver CSE-PDFF based on 5.0T and 3.0T,1.5T MR scanner were both good(ICC=0.989,0.992,both P＜0.001).The overall consistencies of CSE-PDFF based on 5.0T MR and MRS-PDFF based on 5.0T and 1.5T MR were both good(both ICC＞0.75,both P＜0.001).CSE-PDFF had good consistency with MRS-PDFF based on same 5.0T MR scanner(ICC=0.988,P＜0.001),and CSE-PDFF based on 5.0T had good consistency with MRS-PDFF based on 1.5T MR scanner(ICC=0.978,P＜0.001).Conclusion 5.0T MRI had high value for quantifying liver PDFF.

Objective To observe the consistency of 5.0T and 1.5T MR spectroscopy(MRS)for quantitating proton density fat fraction(PDFF)of liver.Methods Lipid emulsion models with lipid content of 0,5％,10％,15％,20％,25％and 30％were prepared.1H-MRS were collected using 5.0T and 1.5T MR scanners,respectively,and PDFF were obtained with jMRUI software.Totally 23 people,including 11 cases of fatty liver and 12 healthy adults were prospectively collected,and volume of interest(VOI)in the liver were selected to acquire 1H-MRS,and PDFF were obtained with jMRUI software and corresponding workstation,respectively.The consistencies of PDFF measured with different methods were analyzed.Results PDFF of lipid emulsion models with lipid content of 0,5％,10％,15％,20％,25％and 30％measured with jMRUI software and workstations based on 5.0T and 1.5T 1H-MRS all had good consistencies and being positively correlated,so were PDFF of liver tissue measured with jMRUI software and workstations based on 5.0T and 1.5T 1H-MRS.Conclusion 5.0T and 1.5T 1H-MRS had good consistency for quantitating liver PDFF.Measuring liver PDFF with workstation in clinical practice was helpful to simplifying workflow.

OBJECTIVE: To explore biomarkers for early auxiliary diagnosis of pneumoconiosis in coal workers(CWP) and its clinical significance. METHODS: Sixty-nine male coal miners exposed to dust were selected as control group, and sixty-seven CWP male patients were chosen as CWP group by purposive sampling method. Serum samples were collected from subjects of the two groups. The levels of malonaldehyde(MDA) and superoxide dismutase(SOD) were determined by colorimetric method. The enzyme-linked immunosorbent assay was used to measure the level of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α). The acetylcholinesterase(AChE) activity was determined by modified Ellman method. The logistic regression model was used to analyze the risk factors of CWP. The receiver operating characteristic(ROC) curve was established to analyze the sensitive indicators in the pathogenesis of CWP. RESULTS: The serum SOD activity decreased(median: 65.1 vs 59.2 kU/L, P<0.05), and the MDA, IL-6 and TNF-α levels increased in the CWP group(median: 4.92 vs 6.68 μmol/L, 129.82 vs 163.18 ng/L, 63.90 vs 70.93 ng/L, P<0.05) compared with the control group. The logistic regression analysis results showed that AChE was the protective factor of CWP, while age, chronic respiratory symptoms, IL-6 and MDA were the risk factors of CWP(P<0.05). The ROC curve showed that IL-6 and MDA can be used as early indicators for the diagnosis of CWP in dust-exposed workers. CONCLUSION: The serum IL-6 and MDA levels can be used as biomarkers for early auxiliary diagnosis of CWP.

Cerebrospinal fluid proteomics, a branch of proteomics, is aimed to separate different types of cerebrospinal fluid proteins and identify differentially expressed protein sites through core analysis techniques.Since cerebrospinal fluid is directly connected with extracellular fluid of brain tissue, the abnormal change in the central nervous system could influence the composition of cerebrospinal fluid, such as peptides and proteins.Cerebrospinal fluid proteomics research gives insight into understanding of physiological and pathological changes of central nervous system(CNS), which is a supplement of cytological examination and biochemical test for CNS, and the technology provides a support for diagnosis and treatment of CNS diseases.Detecting cerebrospinal fluid proteomics is of great importance for the diagnosis,treatment and prognosis of CNS diseases.

Objective To investigate the relationship between electrical stimulus intensity and postopera-tive complications of puncture trigeminal ganglion radiofrequency thermocoagulation (PTGRT). Methods 86 pa-tients with trigeminal neuralgia (TN) on the second and the third branch underwent trigeminal ganglion radiofre-quency thermocoagulation in Xuanwu Hospital , Capital Medical University from June 2013 to December 2015 enrolled in this study. Electrical stimulus intensity in surgery and postoperative pain VAS score , numbness score, masseter muscles score and complications were recorded at 0, 24 and 48 hours post-surgery. Correlations among electrical stimulus intensity in surgery and postoperative pain VAS score,numbness score, masseter mus-cles score were analyzed. Result The 86 patients had different degrees of facial numbness , some patients had different degrees of masseter weakness , and 2 patients had mild sialorrhea in two days after PTGRT without serve complications. Eighty-three patients (96.51%) had no pain, and VAS score wass 0 at 0, 24 and 48 hours post-PTGRT. Electrical stimulus intensity in surgery had apparent negative correlation with numbness score at 0 , 24 and 48 hours popst-PTGRT (P < 0.01), with negative correlation with masseter muscles decreasing at 48 hours post-PTGRT (P < 0.05). Conclusion Suitable temperature and time in PTGRT were needed to be chose ac-cording to the electrical stimulus intensity.

Objective To analyze and study the connections between hypovolemia and lower extremity deep venous thrombosis (LDVT)in patients with cerebral infarction. Methods A total of 504 hospitalized patients with cerebral in-farction were selected. According to the comparison between infarction group and non-infarction group, ROC curves of urea nitrogen/creatinine ratio, plasma osmotic pressure, combined index of the two indices above and D-dimer were created, cut-off value of the indices above was calculated, and sensitivity and specificity were compared. Results Analysis on the results of ROC curves showed ROC area under the curve of urea nitrogen/creatinine ratio in the diag-nosis of LDVT in 10-14 days after admission was 0.788(95%CI 0.727-0.848),the optimal diagnostic cut-off point was 101.705, the sensitivity was 58%, and the specificity was 88.7%; ROC area under the curve of plasma osmotic pres-sure was 0.892 (95%CI 0.836-0.949), the optimal diagnostic cut-off point was 305.77 mmol/L, the sensitivity was 85.5%, and the specificity was 90.8%; ROC area under the curve of the combined index was 0.895 (95%CI 0.837-0.952); ROC area under the curve of D-dimer was 0.883(95%CI0.832-0.935), the optimal diagnostic cut-off point was 3.055 ug/L,the sensitivity was 85.5%, and the specificity was 82.1%. Conclusion Combined index of urea nitro-gen/creatinine ratio and plasma osmotic pressure in the diagnosis of LVDT is better than D-dimer, which is beneficial for early diagnosis.