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.

Objective:To compare the differences in chemical compositions before and after processing by different processing methods; To optimize the processing method of Atractylodes lancea Rhizoma.Methods:Atractylodes lancea Rhizoma was processed by stir-frying with bran and treating with rice washing water. The volatile and non-volatile components of raw Atractylodes lancea Rhizoma, bran-fried Atractylodes lancea Rhizoma and rice washing water treated Atractylodes lancea Rhizome were qualitatively analyzed by headspace gas chromatography-mass spectrometry (HS-GC-MS) and ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), and the differences in chemical composition before and after processing were compared.Results:The volatile components of the three different products were determined to have 18 common components, such as agarospirol, β-eudesol, etc. In addition, 86 non-volatile components were determined. The peak area response value of atractylodin, the index component prescribed by pharmacopoeia, decreased after processing, but there was little difference in bran stir-frying and rice-washed water frying.Conclusions:Different processing methods have certain effects on the chemical composition of Atractylodes lancea Rhizoma. Among them, the bran-frying method is superior in improving the quality of preparations, reducing production costs and improving production efficiency. The bran-fried product can be used as raw material for preparation production.

BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

OBJECTIVE: To explore decompression strategies for lateral lumbar spinal stenosis under unilateral biportal endoscopy (UBE) assistance. METHODS: A clinical data of 86 patients with lateral lumbar stenosis treated with UBE-assisted intervertebral decompression between September 2022 and December 2023 was retrospectively analyzed. There were 42 males and 44 females with an average age of 63.6 years (range, 45-79 years). The disease duration ranged from 6 to 14 months (mean, 8.5 months). Surgical levels included L _{2, 3} in 3 cases, L _{3, 4} in 26 cases, L _{4, 5} in 42 cases, and L ₅, S ₁ in 15 cases. According to Lee's grading system, there were 21 cases of grade 1, 37 cases of grade 2, and 28 cases of grade 3 for lumbar spinal stenosis. Based on the location of stenosis and clinical symptoms, the 33 cases underwent interlaminar approach, 7 cases underwent interlaminar approach with auxiliary third incision, 26 cases underwent contralateral inclinatory approach, and 20 cases underwent paraspinal approach; then, the corresponding decompression procedures were performed. Visual analogue scale (VAS) score was used to evaluate lower back/leg pain before operation and at 1 and 3 months after operation, while Oswestry disability index (ODI) was used to evaluate spinal function. At 3 months after operation, the effectiveness was evaluated using the modified MacNab evaluation criteria. The spinal stenosis and decompression were evaluated based on Lee's grading system using lumbar MRI before operation and at 3 months after operation. RESULTS: All procedures were successfully completed with mean operation time of 95.1 minutes (range, 57-166 minutes). Dural tears occurred in 2 cases treated with interlaminar approach with auxiliary third incision. All incisions healed by first intention. All patients were followed up 3-10 months (mean, 5.9 months). The clinical symptoms of the patients relieved to varying degrees. The VAS scores and ODI of lower back and leg pain at 1 and 3 months after operation significantly improved compared to preoperative levels ( P<0.05), and the indicators at 3 months significantly improved than that at 1 month ( P<0.05). According to the modified MacNab evaluation criteria, the effectiveness at 3 months after operation was rated as excellent in 52 cases, good in 21 cases, and poor in 13 cases, with an excellent and good rate of 84.9%. No lumbar instability was detected on flexion-extension X-ray films during follow-up. The Lee's grading of lateral lumbar stenosis at 2 days after operation showed significant improvement compared to preoperative grading ( P<0.05). CONCLUSION For lateral lumbar spinal stenosis, UBE-assisted decompression of the spinal canal requires the selection of interlaminar approach, interlaminar approach with auxiliary third incision, contralateral inclinatory approach, and paraspinal approach based on preoperative imaging findings and clinical symptoms to achieve better effectiveness.
Humans ; Spinal Stenosis/diagnostic imaging* ; Female ; Male ; Middle Aged ; Decompression, Surgical/methods* ; Aged ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Retrospective Studies ; Treatment Outcome

Objective To investigate the high-risk factors associated with acute postoperative hypertension (APH) following laparoscopic sleeve gastrectomy(LSG) in obese patients and to establish a predictive model. Methods A retrospective analysis was conducted on clinical data and laboratory parameters of obese patients who underwent LSG at Department of Metabolic Surgery in our hospital from August 2021 to December 2023. Logistic-LASSO regression analysis was used to identify independent risk factors for APH. A nomogram predictive model was developed based on these factors. The predictive performance and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, Bootstrap resampling, calibration curve, Hosmer-Lemeshow (H-L) test, decision curve analysis (DCA), and clinical impact curve (CIC). Results The incidence of APH was 55.90%. Body mass index (BMI), platelet count, globulin, uric acid, sodium, fibrinogen, fasting blood glucose, and preoperative diastolic pressure had potential predictive value. Among them, BMI (OR=1.066, 95% CI: 1.003-1.137, P=0.046), platelet count (OR=0.994, 95% CI: 0.998-0.999, P=0.027), fibrinogen (OR=1.943, 95% CI: 1.128-3.479, P=0.02), and preoperative diastolic blood pressure (OR=0.953, 95% CI: 0.918-0.985, P = 0.006) were identified as independent high-risk factors. The area under the curve (AUC) of the nomogram was 0.783 (95% CI: 0.711-0.855), with a sensitivity of 0.817 and a specificity of 0.689. The AUC based on Bootstrap resampling was 0.776 (95% CI: 0.702-0.849). The H-L test yielded P>0.05, and the calibration curve showed good model fit. Both DCA and CIC demonstrated favorable screening efficiency. Conclusions BMI, platelet count, fibrinogen, and preoperative diastolic blood pressure are independent high-risk factors for APH following LSG. The developed nomogram model exhibits good predictive performance and clinical applicability, providing a valuable tool for early screening and prevention of APH in LSG patients.

ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection， as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022， among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment （2022 edition） were enrolled， and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system， with stages 0 — 4 for inflammation grade （G） and stages 0 — 4 for fibrosis degree （S）， and the patients were divided into groups based on the presence of significant necroinflammation （≥G2） and significant liver fibrosis （≥S2）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors， and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled， among whom 61 （22.5%） had significant necroinflammation （≥G2） and 124 （45.8%） had significant liver fibrosis （≥S2）. The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L （for male patients） or ≥19 U/L （for female patients） （odds ratio ［OR］=2.69， 95% confidence interval ［CI］： 1.39 — 5.21， P=0.003）， HBV DNA ≥2 000 IU/mL （OR=2.75， 95%CI： 1.38 — 5.48， P=0.004）， and liver stiffness measurement （LSM） ≥6.0 kPa （OR=4.57， 95%CI： 2.17 — 9.62， P<0.001） were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL （OR=1.82， 95%CI： 1.01 — 3.32， P=0.049） and LSM ≥6.0 kPa （OR=2.06， 95%CI： 1.23 — 3.43， P=0.006） were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection， a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.

The cognitive impairment of diabetes mellitus type 2(T2DM)is closely related to neurovascular coupling(NVC)changes,but the exact mechanism remains unclear.Functional MRI(fMRI)technology were able to jointly analyze NVC changes of T2DM,providing new ideas for revealing the mechanism of cognitive dysfunction caused by T2DM.The progresses of fMRI for exploring NVC changes in T2DM were reviewed in this article.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Objective:To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender.Methods:This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient ( ICC). Results:A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions:Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

Perioperative neurocognitive disorders(PND)are common perioperative diseases,which bring heavy burden to patients and society.Due to complex pathogenesis of PND and the lack of relia-ble diagnosis and intervention means,and electroencephalography(EEG)and magnetic resonance imaging(MRI)have the advantage of providing objective indicators,so their application in the study of PND has gradually become a hot topic.In this review,the intraoperative processed EEG indices,EEG spectral analy-sis,EEG functional connectivity analysis,EEG nonlinear dynamics analysis,and perioperative MRI analysis in patients with PND are reviewed,aiming to explore the clinical value of EEG and MRI in predic-ting and diagnosing PND.