Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective:To explore the value of amide proton transfer weighted imaging (APTWI) combined with human epidermal growth factor receptor 2 (HER2) expression in predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer.Methods:The study was a cross-sectional study. Clinicopathological [estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 status, and molecular subtypes] and imaging data were retrospectively analyzed in 100 female patients who had invasive ductal carcinoma of the breast confirmed pathologically by preoperative puncture in the Henan Cancer Hospital from May 2023 to May 2024. All patients underwent MRI, including enhanced MRI, APTWI, and diffusion-weighted imaging (DWI) before NAC. The reference enhanced MRI images were segmented into lesions using the threshold extraction method, and the three-dimensional region of interest within the tumor was automatically outlined by the software and replicated in the amide proton transfer map generated by APTWI and the apparent diffuse coefficient (ADC) map generated by DWI. The magnetization transfer ratio asymmetry (MTRasym) value and the ADC value were measured, respectively. Tumor response to NAC was assessed using the Miller-Payne grading system, where Grade 5 indicated pCR and Grades 1-4 were classified as non-pCR. Independent sample t-tests and χ2 tests were used to compare clinical pathological and imaging parameters between pCR and non-pCR patients. Statistically significant variables were included in multivariate logistic regression to identify independent predictors of pCR. The diagnostic performance of individual and combined indicators for pCR was evaluated using receiver operating characteristic curves and the area under the curve (AUC). DeLong′s test was used to compare AUCs. Results:There were 39 pCR and 61 non-pCR patients. Significant differences were observed between the pCR and non-pCR patients in molecular subtypes, ER, PR, HER2, and Ki-67 statuses ( P<0.05). Pre-treatment MTRasym values were significantly higher in the pCR patients compared to the non-pCR patients ( P=0.005), whereas ADC values showed no statistical difference ( P=0.372). Multivariate logistic regression analysis showed HER2 positivity ( OR=5.87, 95% CI 1.99-17.30, P=0.001) and MTRasym values>2.61% (OR=4.39, 95% CI 1.37-14.08, P=0.013) was independent predictors of pCR after NAC. HER2 positivity combined with MTRasym value>2.61% predicted pCR after NAC in breast cancer with AUC of 0.819, which was superior to HER2 positivity and MTRasym value alone in predicting efficacy ( Z=3.91, P<0.001; Z=2.63, P=0.009). Conclusions:The MTRasym value of pre-treatment APTWI is valuable in predicting pCR after NAC in breast cancer. APTWI combined with HER2 expression status can further enhance the predictive efficacy.

Objective To investigate the value of MRI radiomics for the preoperative noninvasive prediction of isocitrate dehydrogenase(IDH)mutation status in glioma.Methods Totally,306 glioma patients were retrospectively selected.All patients were randomly assigned into training group(n=214)and validation group(n=92)at a ratio of 7∶3.Region of interest(ROI)was manually delineated by two radiologists independently on the fluid attenuated inversion recovery(FLAIR)and contrast enhanced(CE)MRI images for obtaining whole volume of interest(VOI)of lesion.A total of 851 radiomics features were extracted from the VOI,respectively.The least absolute shrinkage and selection operator(LASSO)method was used for features dimension reduction combing 10-fold cross validation.Three Radiomics score(Radscore)were calculated by linear combination of retained features and their corresponding coefficients.The optimal Radscore and clinical characteristics were incorporated to perform logistic regression analysis for establishing the IDH mutation status noninvasive prediction model.A nomogram was plotted for realizing the visualization of model.The receiver operating characteristic(ROC)curve was plotted to evaluate the prediction performance of model.The calibration and clinical utility of the model were evaluated by calibration curve and decision curve.Results The area under the curve(AUC)of Radscore-combined based on combination of two sequences was 0.856 in the training group,which was superior to the Radscore-CE(AUC=0.821),Radscore-FLAIR(AUC=0.766)from single sequence,with consistent result in the validation group.The addition of clinical characteristics to the model improved predictive value with AUC,sensitivity and specificity of 0.898,79.59％,90.52％in the training group.Conclusion The radiomics model based on FLAIR and CE MRI contributes to preoperative noninvasive prediction of IDH mutation status in glioma.The combination of multi-sequence and the addition of clinical characteristics can improve the prediction performance.

Objective:To analyze the sequencing results, protein structure model, and impact of mutations on the dynamic stability of glycosyltransferase (GTA) in a case with Aw26 blood group subtype.Methods:ABO phenotype was determined by serological testing (anti-A, anti-B, anti-H, and reverse typing). Potential variant of the ABO gene was identified by Sanger sequencing, and the haploid sequence of the variant site was analyzed by TOPOT-A cloning. Molecular models of the GTA was generated by PyMol, and 100-ns molecular dynamics (MD) was simulated with GROMACS software to assess the conformational stability using root mean square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bonding, and binding free energy.Results:Serological assays confirmed the proband as an Aw subtype, whose genotype was identified as ABO*Aw.26/ABO*O.01.02 with variants including p. Pro156Leu, p. Arg176His and p. Pro354ArgfsTer23. Haploid sequencing validated the results of direct sequencing. Molecular modeling showed that the p. Arg176His variant could reduce water-mediated hydrogen bonds from six (wild-type) to one (variant). MD simulation revealed the wild type system could achieve equilibrium within 10 ns (mean RMSD ≈ 0.30 nm), whilst the mutant system required 50 ns to equilibrate and exhibited greater fluctuation (mean RMSD ≈ 0.40 nm). Root mean square fluctuation (RMSF) analysis confirmed significantly increased flexibility in the mutant′s N-terminal loop (residues 63-76). The mutant Rg displayed an expansion-contraction transition within 0 ~ 40 ns, and its SASA value has increased. The number of hydrogen bonds and binding energy of the mutant had decreased (wild-type: 5 to 8, binding energy: -11.53 kcal/mol; mutant: 2 to 5, binding energy: -8.52 kcal/mol). Conclusion:An Aw26 subtype was identified. The p. Arg176His and p. Pro354Argfs*23p variants could synergistically compromise the structural stability of GTA and its substrate binding capacity by disrupting the hydrogen-bond network, increasing local flexibility, and reducing the overall conformational stability.

OBJECTIVE T o explore the value of targeted next-generation sequencing(t-NGS)in diagnosis of respir-atory tract pathogens through meta-analysis so as to provide reference for clinical application.METHODS PubMed database,Web of Science database,Wanfang database,CNKI database and Sinomed database were retrieved,and the time period of retrieval ranged from Jan.2010 to May 2024.The literatures were screened out based on the es-tablished standards.The quality was assessed by QU ADAS-2,the risk of bias graph was drawn by Revman 5.4,and the statistical analysis was performed by Stata 16.0.RESULTS A total of 9 literatures were included in the study.The result of meta-analysis showed that the heterogeneity test Q for sensitivity was 268.21,P＜0.01,I2=97.02％,with the heterogeneity test Q for specificity 210.04,P＜0.01,I2=96.19％,the combined sensitivity 0.88(95％CI:0.62 to 0.97),combined specificity 0.68(95％CI:0.41 to 0.86),combined positive likelihood ratio 2.72(95％CI:1.44 to 5.15),combined negative likelihood ratio 0.18(95％CI:0.06 to 0.53),combined diagno-sis score 2.74(95％CI:1.68 to 3.80),and combined diagnostic odds ratio 15.44(95％CI:5.34 to 44.66).The area under synthesize receiver operating characteristic(SROC)curve(AUC)was 0.85(95％CI:0.82 to 0.88).The result of Deeks funnel plot showed that P was 0.99,indicating that there was no obvious publication bias.CONCLUSIONS The sensitivity of tNGS is high in detection of the pathogens causing acute respiratory tract infection,the specificity needs to be improved,but its comprehensive ability is satisfactory.It has certain val-ue in early clinical diagnosis.

OBJECTIVE: To analyze the sequencing results, protein structure model, and impact of mutations on the dynamic stability of glycosyltransferase (GTA) in a case with Aw26 blood group subtype. METHODS: ABO phenotype was determined by serological testing (anti-A, anti-B, anti-H, and reverse typing). Potential variant of the ABO gene was identified by Sanger sequencing, and the haploid sequence of the variant site was analyzed by TOPOT-A cloning. Molecular models of the GTA was generated by PyMol, and 100-ns molecular dynamics (MD) was simulated with GROMACS software to assess the conformational stability using root mean square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bonding, and binding free energy. RESULTS: Serological assays confirmed the proband as an Aw subtype, whose genotype was identified as ABO*Aw.26/ABO*O.01.02 with variants including p.Pro156Leu, p.Arg176His and p.Pro354ArgfsTer23. Haploid sequencing validated the results of direct sequencing. Molecular modeling showed that the p.Arg176His variant could reduce water-mediated hydrogen bonds from six (wild-type) to one (variant). MD simulation revealed the wild type system could achieve equilibrium within 10 ns (mean RMSD ≈ 0.30 nm), whilst the mutant system required 50 ns to equilibrate and exhibited greater fluctuation (mean RMSD ≈ 0.40 nm). Root mean square fluctuation (RMSF) analysis confirmed significantly increased flexibility in the mutant's N-terminal loop (residues 63-76). The mutant Rg displayed an expansion-contraction transition within 0 ~ 40 ns, and its SASA value has increased. The number of hydrogen bonds and binding energy of the mutant had decreased (wild-type: 5 to 8, binding energy: -11.53 kcal/mol; mutant: 2 to 5, binding energy:-8.52 kcal/mol). CONCLUSION An Aw26 subtype was identified. The p.Arg176His and p.Pro354Argfs*23p variants could synergistically compromise the structural stability of GTA and its substrate binding capacity by disrupting the hydrogen-bond network, increasing local flexibility, and reducing the overall conformational stability.
ABO Blood-Group System/chemistry* ; Humans ; Molecular Dynamics Simulation ; Models, Molecular ; Mutation ; Genotype ; Protein Conformation ; Glycosyltransferases/chemistry* ; Male

This article reports a case of multiple cranial nerve injury after gamma knife radiosurgery treated with acupuncture and moxibustion combined with rehabilitation therapy. The patient presented with weakness of facial and tongue muscles, hoarseness, choking on water, and swallowing difficulties. The syndrome was attributed to qi and blood deficiency, and blood stasis obstructing the collaterals. The treatment principle focused on replenishing qi and blood, promoting blood circulation and unblocking collaterals. Yintang (GV24⁺), Lianquan (CV23), Qihai (CV6), Guanyuan (CV4), and Cuanzhu (BL2), Yangbai (GB14), Jingming (BL1), Sizhukong (TE23), Yingxiang (LI20), Sibai (ST2), Juliao (ST3), Quanliao (SI18), Dicang (ST4), Jiache (ST6), Xiaguan (ST7), Taiyang (EX-HN5) on the affected side, bilateral Jinjin (EX-HN12), Yuye (EX-HN13), Hegu (LI4), Zusanli (ST36), Sanyinjiao (SP6), Tianshu (ST25) were selected. Among these, bilateral Jinjin (EX-HN12) and Yuye (EX-HN13) were treated with pricking, Dicang (ST4) and Jiache (ST6) on the affected side were connected to an electroacupuncture device, and warming acupuncture was applied at Guanyuan (CV4). Rehabilitation therapy and electromyographic biofeedback were also incorporated. The treatments were given 2-3 times a week. After 18 months of intermittent treatment, the patient reported significant improvement, House Brackmann (H-B) facial nerve function grade was Ⅳ, and Sunnybrook facial nerve rating scale score was 53 points. After 2-month of follow-up, the patient reported normal swallowing ability and restored social engagement.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Cranial Nerve Diseases/therapy*